Serine Protease Inhibitors in Ticks: An Overview of Their Role in Tick Biology and Tick-Borne Pathogen Transmission

Adrien Blisnick1, Thierry Foulon2, Sarah Bonnet1
1Biologie moléculaire et immunologie parasitaires et fongiques
2Biosynthèse des Signaux Peptidiques [IBPS]

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Tài liệu tham khảo

Abreu, 2014, RmKK, a tissue kallikrein inhibitor from Rhipicephalus microplus eggs, Biochem. Biophys. Res. Commun., 449, 69, 10.1016/j.bbrc.2014.04.154

Adakal, 2013, Tick control practices in Burkina Faso and acaricide resistance survey in Rhipicephalus (Boophilus) geigyi (Acari: Ixodidae), Exp. Appl. Acarol., 59, 483, 10.1007/s10493-012-9610-5

Aird, 2003, Hemostasis and irreducible complexity, J. Thromb. Haemost., 1, 227, 10.1046/j.1538-7836.2003.00062.x

Alim, 2012, A hemocyte-derived Kunitz–BPTI-type chymotrypsin inhibitor, HlChI, from the Ixodid tick Haemaphysalis longicornis, plays regulatory functions in tick blood-feeding processes, Insect Biochem. Mol. Biol., 42, 925, 10.1016/j.ibmb.2012.09.005

Anastopoulos, 1991, Anticoagulant in the tick Ixodes holocyclus, Aust. Vet. J., 68, 366, 10.1111/j.1751-0813.1991.tb00740.x

Anderson, 2008, Exploring the mialome of ticks: an annotated catalogue of midgut transcripts from the hard tick, Dermacentor variabilis (Acari: Ixodidae), BMC Genomics, 9, 552, 10.1186/1471-2164-9-552

Andoh, 2010, Bradykinin increases the secretion and expression of endothelin-1 through kinin B2 receptors in melanoma cells, Peptides, 31, 238, 10.1016/j.peptides.2009.12.003

Andreotti, 2012, Protective immunity against tick infestation in cattle vaccinated with recombinant trypsin inhibitor of Rhipicephalus microplus, Vaccine, 30, 6678, 10.1016/j.vaccine.2012.08.066

Andreotti, 2002, BmTI antigens induce a bovine protective immune response against Boophilus microplus tick, Int. Immunopharmacol., 2, 557, 10.1016/S1567-5769(01)00203-X

Andreotti, 2001, Serine proteinase inhibitors from eggs and larvae of tick Boophilus microplus: purification and biochemical characterization, J. Protein Chem., 20, 337, 10.1023/A:1012242817869

Armstrong, 1985, An alpha 2-macroglobulinlike activity in the blood of chelicerate and mandibulate arthropods, J. Exp. Zool., 236, 1, 10.1002/jez.1402360102

Ascenzi, 2003, The bovine basic pancreatic trypsin inhibitor (Kunitz inhibitor): a milestone protein, Curr. Protein Pept. Sci., 4, 231, 10.2174/1389203033487180

Assumpção, 2016, In vitro mode of action and anti-thrombotic activity of boophilin, a multifunctional kunitz protease inhibitor from the midgut of a tick vector of Babesiosis, Rhipicephalus microplus, PLoS Negl. Trop. Dis., 10, e0004298, 10.1371/journal.pntd.0004298

Batista, 2010, A new factor Xa inhibitor from Amblyomma cajennense with a unique domain composition, Arch. Biochem. Biophys., 493, 151, 10.1016/j.abb.2009.10.009

Bissinger, 2011, Synganglion transcriptome and developmental global gene expression in adult females of the American dog tick, Dermacentor variabilis (Acari: Ixodidae), Insect Mol. Biol., 20, 465, 10.1111/j.1365-2583.2011.01086.x

Branco, 2016, Amblyomin-X having a Kunitz-type homologous domain, is a noncompetitive inhibitor of FXa and induces anticoagulation in vitro and in vivo, Biochim. Biophys. Acta, 1864, 1428, 10.1016/j.bbapap.2016.07.011

Brossard, 2004, Tick immunobiology, Parasitology, 129, S161, 10.1017/S0031182004004834

Buresová, 2006, A comparison of Chryseobacterium indologenes pathogenicity to the soft tick Ornithodoros moubata and hard tick Ixodes ricinus, J. Invertebr. Pathol., 93, 96, 10.1016/j.jip.2006.05.006

Buresova, 2009, IrAM—an α2-macroglobulin from the hard tick Ixodes ricinus: characterization and function in phagocytosis of a potential pathogen Chryseobacterium indologenes, Dev. Comp. Immunol., 33, 489, 10.1016/j.dci.2008.09.011

Cao, 2013, Characterization of a new Kunitz-type serine protease inhibitor from the hard tick Rhipicephalus hemaphysaloides, Arch. Insect Biochem. Physiol., 84, 104, 10.1002/arch.21118

Caughey, 2007, Mast cell tryptases and chymases in inflammation and host defense, Immunol. Rev., 217, 141, 10.1111/j.1600-065X.2007.00509.x

Ceraul, 2011, A Kunitz protease inhibitor from Dermacentor variabilis, a vector for spotted fever group rickettsiae, limits Rickettsia montanensis invasion, Infect. Immun., 79, 321, 10.1128/IAI.00362-10

Ceraul, 2007, New tick defensin isoform and antimicrobial gene expression in response to Rickettsia montanensis challenge, Infect. Immun., 75, 1973, 10.1128/IAI.01815-06

Ceraul, 2008, Functional characterization and novel rickettsiostatic effects of a Kunitz-type serine protease inhibitor from the tick Dermacentor variabilis, Infect. Immun., 76, 5429, 10.1128/IAI.00866-08

Cerenius, 2010, High sequence variability among hemocyte-specific Kazal-type proteinase inhibitors in decapod crustaceans, Dev. Comp. Immunol., 34, 69, 10.1016/j.dci.2009.08.005

Chalaire, 2011, Amblyomma americanum (L.) (Acari: Ixodidae) tick salivary gland serine protease inhibitor (serpin) 6 is secreted into tick saliva during tick feeding, J. Exp. Biol., 214, 665, 10.1242/jeb.052076

Chand, 2004, Structure-function analysis of the reactive site in the first Kunitz-type domain of human tissue factor pathway inhibitor-2, J. Biol. Chem., 279, 17500, 10.1074/jbc.M400802200

Chmelar, 2016, Sialomes and mialomes: a systems-biology view of tick tissues and tick-host interactions, Trends Parasitol., 32, 242, 10.1016/j.pt.2015.10.002

Chmelar, 2011, A tick salivary protein targets cathepsin G and chymase and inhibits host inflammation and platelet aggregation, Blood, 117, 736, 10.1182/blood-2010-06-293241

Chudzinski-Tavassi, 2010, A new tick Kunitz-type inhibitor, amblyomin-X, induces tumor cell death by modulating genes related to the cell cycle and targeting the ubiquitin-proteasome system, Toxicon, 56, 1145, 10.1016/j.toxicon.2010.04.019

Ciprandi, 2006, Boophilus microplus: its saliva contains microphilin, a small thrombin inhibitor, Exp. Parasitol., 114, 40, 10.1016/j.exppara.2006.02.010

Coleman, 1997, Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice, Cell, 89, 1111, 10.1016/S0092-8674(00)80298-6

Cotté, 2008, Transmission of Bartonella henselae by Ixodes ricinus, Emerging Infect. Dis., 14, 1074, 10.3201/eid1407.071110

Cotté, 2014, Differential expression of Ixodes ricinus salivary gland proteins in the presence of the Borrelia burgdorferi sensu lato complex, J. Proteomics, 96, 29, 10.1016/j.jprot.2013.10.033

The two-disulphide intermediates and the folding pathway of reduced pancreatic trypsin inhibitor167199 CreightonT. E. 10.1016/0022-2836(75)90389-71185779J. Mol. Biol.951975

Dai, 2012, Evolution, expansion and expression of the Kunitz/BPTI gene family associated with long-term blood feeding in Ixodes scapularis, BMC Evol. Biol., 12, 4, 10.1186/1471-2148-12-4

Dantas-Torres, 2012, Ticks and tick-borne diseases: a One Health perspective, Trends Parasitol., 28, 437, 10.1016/j.pt.2012.07.003

Decrem, 2009, Ir-CPI, a coagulation contact phase inhibitor from the tick Ixodes ricinus, inhibits thrombus formation without impairing hemostasis, J. Exp. Med., 206, 2381, 10.1084/jem.20091007

De Meneghi, 2016, Experiences in tick control by Acaricide in the traditional cattle sector in Zambia and Burkina Faso: possible environmental and public health implications, Front Public Health, 4, 239, 10.3389/fpubh.2016.00239

Drewes, 2012, Actions of the Kunitz-type serine protease inhibitor amblyomin-X on VEGF-A-induced angiogenesis, Toxicon, 60, 333, 10.1016/j.toxicon.2012.04.349

Egekwu, 2014, Transcriptome of the female synganglion of the black-legged tick Ixodes scapularis (Acari: Ixodidae) with comparison between Illumina and 454 systems, PLoS ONE, 9, e102667, 10.1371/journal.pone.0102667

Ehebauer, 2002, Identification of extrinsic blood coagulation pathway inhibitors from the tick Ornithodoros savignyi (Acari: Argasidae), Exp. Parasitol., 101, 138, 10.1016/S0014-4894(02)00102-9

Fogaça, 2006, Ixodidin, a novel antimicrobial peptide from the hemocytes of the cattle tick Boophilus microplus with inhibitory activity against serine proteinases, Peptides, 27, 667, 10.1016/j.peptides.2005.07.013

Francischetti, 2011, An insight into the sialotranscriptome and proteome of the coarse bontlegged tick, Hyalomma marginatum rufipes, J. Proteomics, 74, 2892, 10.1016/j.jprot.2011.07.015

Francischetti, , Tick saliva is a potent inhibitor of endothelial cell proliferation and angiogenesis, Thromb. Haemost., 94, 167

Francischetti, 2004, Penthalaris, a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis, Thromb. Haemost., 91, 886, 10.1160/TH03-11-0715

Francischetti, , The transcriptome of the salivary glands of the female western black-legged tick Ixodes pacificus (Acari: Ixodidae), Insect Biochem. Mol. Biol., 35, 1142, 10.1016/j.ibmb.2005.05.007

Francischetti, 2009, The role of saliva in tick feeding, Front. Biosci., 14, 2051, 10.2741/3363

Francischetti, 2002, Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffolds for the inhibition of factor VIIa/tissue factor complex, Blood, 99, 3602, 10.1182/blood-2001-12-0237

Franta, 2010, Dynamics of digestive proteolytic system during blood feeding of the hard tick Ixodes ricinus, Parasit. Vectors, 3, 119, 10.1186/1756-3305-3-119

Fredslund, 2008, Structure of and influence of a tick complement inhibitor on human complement component 5, Nat. Immunol., 9, 753, 10.1038/ni.1625

Gao, 2011, Characterization of the anticoagulant protein Rhipilin-1 from the Rhipicephalus haemaphysaloides tick, J. Insect Physiol., 57, 339, 10.1016/j.jinsphys.2010.12.001

Garcia, 2014, The sialotranscriptome of Amblyomma triste, Amblyomma parvum and Amblyomma cajennense ticks, uncovered by 454-based RNA-seq, Parasit. Vectors, 7, 430, 10.1186/1756-3305-7-430

Gaspar, 1996, Isolation and characterization of an anticoagulant from the salivary glands of the tick, Ornithodoros savignyi (Acari: Argasidae), Exp. Appl. Acarol., 20, 583, 10.1007/BF00052809

Grzesiak, 2000, Substitutions at the P(1) position in BPTI strongly affect the association energy with serine proteinases, J. Mol. Biol., 301, 205, 10.1006/jmbi.2000.3935

Gubb, 2010, Protease inhibitors and proteolytic signalling cascades in insects, Biochimie, 92, 1749, 10.1016/j.biochi.2010.09.004

Gudderra, 2002, Hemolymph proteins in ticks, J. Insect Physiol., 48, 269, 10.1016/S0022-1910(02)00050-1

Guerrero, 2005, BmiGI: a database of cDNAs expressed in Boophilus microplus, the tropical/southern cattle tick, Insect Biochem. Mol. Biol., 35, 585, 10.1016/j.ibmb.2005.01.020

Hajdusek, 2013, Interaction of the tick immune system with transmitted pathogens, Front. Cell. Infect. Microbiol., 3, 26, 10.3389/fcimb.2013.00026

Heutinck, 2010, Serine proteases of the human immune system in health and disease, Mol. Immunol., 47, 1943, 10.1016/j.molimm.2010.04.020

Hoffmann, 1991, Isolation and characterization of a thrombin inhibitor from the tick Ixodes ricinus, Pharmazie, 46, 209

Horn, 2000, Boophilus microplus anticoagulant protein: an antithrombin inhibitor isolated from the cattle tick saliva, Arch. Biochem. Biophys., 384, 68, 10.1006/abbi.2000.2076

Huntington, 2011, Serpin structure, function and dysfunction, J. Thromb. Haemost., 9, 26, 10.1111/j.1538-7836.2011.04360.x

Huntington, 2000, Structure of a serpin-protease complex shows inhibition by deformation, Nature, 407, 923, 10.1038/35038119

Ibelli, 2014, A blood meal-induced Ixodes scapularis tick saliva serpin inhibits trypsin and thrombin, and interferes with platelet aggregation and blood clotting, Int. J. Parasitol., 44, 369, 10.1016/j.ijpara.2014.01.010

Ibrahim, , Isolation and properties of two forms of thrombin inhibitor from the nymphs of the camel tick Hyalomma dromedarii (Acari: Ixodidae), Exp. Appl. Acarol., 25, 675, 10.1023/A:1016136207308

Ibrahim, , Factor Xa (FXa) inhibitor from the nymphs of the camel tick Hyalomma dromedarii, Comp. Biochem. Physiol. B Biochem. Mol. Biol., 130, 501, 10.1016/S1096-4959(01)00459-6

Imamura, 2005, A serine protease inhibitor (serpin) from Haemaphysalis longicornis as an anti-tick vaccine, Vaccine, 23, 1301, 10.1016/j.vaccine.2004.08.041

Imamura, 2006, Two serine protease inhibitors (serpins) that induce a bovine protective immune response against Rhipicephalus appendiculatus ticks, Vaccine, 24, 2230, 10.1016/j.vaccine.2005.10.055

Irving, 2002, Evidence that serpin architecture intrinsically supports papain-like cysteine protease inhibition: engineering alpha(1)-antitrypsin to inhibit cathepsin proteases, Biochemistry, 41, 4998, 10.1021/bi0159985

Islam, 2009, The Kunitz-like modulatory protein haemangin is vital for hard tick blood-feeding success, PLoS Pathog., 5, e1000497, 10.1371/journal.ppat.1000497

Iwanaga, 2003, Identification and characterization of novel salivary thrombin inhibitors from the ixodidae tick, Haemaphysalis longicornis, Eur. J. Biochem., 270, 1926, 10.1046/j.1432-1033.2003.03560.x

Jablonka, 2015, Identification and mechanistic analysis of a novel tick-derived inhibitor of thrombin, PLoS ONE, 10, e0133991, 10.1371/journal.pone.0133991

Joubert, 1995, Isolation and characterization of an anticoagulant present in the salivary glands of the bont-legged tick, Hyalomma truncatum, Exp. Appl. Acarol., 19, 79, 10.1007/BF00052548

Kato, , Identification and characterization of the plasma kallikrein-kinin system inhibitor, haemaphysalin, from hard tick, Haemaphysalis longicornis, Thromb. Haemost., 93, 359, 10.1160/TH04-05-0319

Kato, , Contribution of the N-terminal and C-terminal domains of haemaphysalin to inhibition of activation of plasma kallikrein-kinin system, J. Biochem., 138, 225, 10.1093/jb/mvi123

Kazimírová, 2002, An inhibitor of thrombin-stimulated blood platelet aggregation from the salivary glands of the hard tick Amblyomma variegatum (Acari: Ixodidae), Exp. Appl. Acarol., 28, 97, 10.1023/A:1025398100044

Kazimirova, 2013, Tick salivary compounds: their role in modulation of host defences and pathogen transmission, Front. Cell. Infect. Microbiol., 3, 43, 10.3389/fcimb.2013.00043

Keller, 1993, Cloning of the cDNA and expression of moubatin, an inhibitor of platelet aggregation, J. Biol. Chem., 268, 5450, 10.1016/S0021-9258(18)53342-1

Kemp, 1989, Vaccination against Boophilus microplus: localization of antigens on tick gut cells and their interaction with the host immune system, Exp. Appl. Acarol., 7, 43, 10.1007/BF01200452

Khan, 2011, Serpin inhibition mechanism: a delicate balance between native metastable state and polymerization, J. Amino Acids, 2011, 606797, 10.4061/2011/606797

Kim, 2016, Target validation of highly conserved Amblyomma americanum tick saliva serine protease inhibitor 19, Ticks Tick Borne Dis., 7, 405, 10.1016/j.ttbdis.2015.12.017

Kim, 2015, Conserved Amblyomma americanum tick Serpin19, an inhibitor of blood clotting factors Xa and XIa, trypsin and plasmin, has anti-haemostatic functions, Int. J. Parasitol., 45, 613, 10.1016/j.ijpara.2015.03.009

Klingler, 1997, Site-specific interaction of thrombin and inhibitors observed by fluorescence correlation spectroscopy, Biophys. J., 73, 2195, 10.1016/S0006-3495(97)78251-1

Koh, 2007, Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bont tick, J. Biol. Chem., 282, 29101, 10.1074/jbc.M705600200

Kopacek, 2010, Tick innate immunity, Adv. Exp. Med. Biol., 708, 137, 10.1007/978-1-4419-8059-5_8

Kopacek, 2000, Characterization of an alpha-macroglobulin-like glycoprotein isolated from the plasma of the soft tick Ornithodoros moubata, Eur. J. Biochem., 267, 465, 10.1046/j.1432-1327.2000.01020.x

Kotal, 2015, Modulation of host immunity by tick saliva, J. Proteomics, 128, 58, 10.1016/j.jprot.2015.07.005

Kotsyfakis, 2015, Deep sequencing analysis of the Ixodes ricinus haemocytome, PLoS Negl. Trop. Dis., 9, e0003754, 10.1371/journal.pntd.0003754

Krowarsch, 2003, Canonical protein inhibitors of serine proteases, Cell. Mol. Life Sci., 60, 2427, 10.1007/s00018-003-3120-x

Kunitz, 1945, Crystallization of a trypsin inhibitor from soybean, Science, 101, 668, 10.1126/science.101.2635.668

Lai, 2004, A thrombin inhibitor from the ixodid tick, Amblyomma hebraeum, Gene, 342, 243, 10.1016/j.gene.2004.07.012

Lang, 2005, Ion channels in cell proliferation and apoptotic cell death, J. Membr. Biol., 205, 147, 10.1007/s00232-005-0780-5

Larsson, 1984, Kinetics of appearance of sulfhydryl groups in alpha 2-macroglobulin on reaction of the inhibitor with amines, Biochemistry, 23, 2802, 10.1021/bi00307a041

Laskowski, 1980, Protein inhibitors of proteinases, Annu. Rev. Biochem., 49, 593, 10.1146/annurev.bi.49.070180.003113

Laskowski, 2000, What can the structures of enzyme-inhibitor complexes tell us about the structures of enzyme substrate complexes?, Biochim. Biophys. Acta, 1477, 324, 10.1016/S0167-4838(99)00284-8

Law, 2006, An overview of the serpin superfamily, Genome Biol., 7, 216, 10.1186/gb-2006-7-5-216

Leboulle, , Characterization of a novel salivary immunosuppressive protein from Ixodes ricinus ticks, J. Biol. Chem., 277, 10083, 10.1074/jbc.M111391200

Leboulle, , Isolation of Ixodes ricinus salivary gland mRNA encoding factors induced during blood feeding, Am. J. Trop. Med. Hyg., 66, 225, 10.4269/ajtmh.2002.66.225

Leger, 1987, Characterization of cuticle-degrading proteases produced by the entomopathogen Metarhizium anisopliae, Arch. Biochem. Biophys., 253, 221, 10.1016/0003-9861(87)90655-2

Liao, 2009, Hemalin, a thrombin inhibitor isolated from a midgut cDNA library from the hard tick Haemaphysalis longicornis, J. Insect Physiol., 55, 165, 10.1016/j.jinsphys.2008.11.004

Lima, 2010, Biochemical characterization of a Kunitz-type inhibitor similar to dendrotoxins produced by Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) hemocytes, Vet. Parasitol., 167, 279, 10.1016/j.vetpar.2009.09.030

Limo, 1991, Purification and characterization of an anticoagulant from the salivary glands of the ixodid tick Rhipicephalus appendiculatus, Exp. Parasitol., 72, 418, 10.1016/0014-4894(91)90088-E

Liu, 2014, Hard tick factors implicated in pathogen transmission, PLoS Negl. Trop. Dis., 8, e2566, 10.1371/journal.pntd.0002566

Liu, 2014, IrSPI, a tick serine protease inhibitor involved in tick feeding and Bartonella henselae infection, PLoS Negl. Trop. Dis., 8, e2993, 10.1371/journal.pntd.0002993

Macedo-Ribeiro, 2008, Isolation, cloning and structural characterisation of Boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick, PLoS ONE, 3, e1624, 10.1371/journal.pone.0001624

Madden, 2004, A proteomics approach to characterizing tick salivary secretions, Exp. Appl. Acarol., 32, 77, 10.1023/B:APPA.0000018316.80224.54

Mans, 2008, Characterization of anti-hemostatic factors in the argasid, Argas monolakensis: implications for the evolution of blood-feeding in the soft tick family, Insect Biochem. Mol. Biol., 38, 22, 10.1016/j.ibmb.2007.09.002

Mans, 2002, Amino acid sequence and structure modeling of savignin, a thrombin inhibitor from the tick, Ornithodoros savignyi, Insect Biochem. Mol. Biol., 32, 821, 10.1016/S0965-1748(01)00169-2

Mast, 1996, Physiological concentrations of tissue factor pathway inhibitor do not inhibit prothrombinase, Blood, 87, 1845, 10.1182/blood.V87.5.1845.1845

Metzker, 2010, Sequencing technologies - the next generation, Nat. Rev. Genet., 11, 31, 10.1038/nrg2626

Miyoshi, 2010, A Kunitz-type proteinase inhibitor from the midgut of the Ixodid tick, Haemaphysalis longicornis, and its endogenous target serine proteinase, Mol. Biochem. Parasitol., 170, 112, 10.1016/j.molbiopara.2009.12.005

Miyoshi, 2007, Molecular and reverse genetic characterization of serine proteinase-induced hemolysis in the midgut of the ixodid tick Haemaphysalis longicornis, J. Insect Physiol., 53, 195, 10.1016/j.jinsphys.2006.12.001

Monteiro, 2005, Targeting exosites on blood coagulation proteases, Anais Acad. Brasil. Ciênc., 77, 275, 10.1590/S0001-37652005000200007

Monteiro, 2005, Ixolaris: a factor Xa heparin-binding exosite inhibitor, Biochem. J., 387, 871, 10.1042/BJ20041738

Morais, 2016, Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell, Mol. Cell. Biochem., 415, 119, 10.1007/s11010-016-2683-4

Motoyashiki, 2003, Isolation of anticoagulant from the venom of tick, Boophilus calcaratus, from Uzbekistan, Thromb. Res., 110, 235, 10.1016/S0049-3848(03)00409-2

Mulenga, 2007, Molecular and expression analysis of a family of the Amblyomma americanum tick Lospins, J. Exp. Biol., 210, 3188, 10.1242/jeb.006494

Mulenga, 2013, Amblyomma americanum tick saliva serine protease inhibitor 6 is a cross-class inhibitor of serine proteases and papain-like cysteine proteases that delays plasma clotting and inhibits platelet aggregation, Insect Mol. Biol., 22, 306, 10.1111/imb.12024

Mulenga, , Three serine proteinases from midguts of the hard tick Rhipicephalus appendiculatus; cDNA cloning and preliminary characterization, Exp. Appl. Acarol., 29, 151, 10.1023/A:1024278402288

Mulenga, 2001, Characterization of two cDNAs encoding serine proteinases from the hard tick Haemaphysalis longicornis, Insect Biochem. Mol. Biol., 31, 817, 10.1016/S0965-1748(00)00187-9

Mulenga, 1999, Molecular characterization of a Haemaphysalis longicornis tick salivary gland-associated 29-kilodalton protein and its effect as a vaccine against tick infestation in rabbits, Infect. Immun., 67, 1652, 10.1128/IAI.67.4.1652-1658.1999

Mulenga, , Four serine proteinase inhibitors (serpin) from the brown ear tick, Rhiphicephalus appendiculatus; cDNA cloning and preliminary characterization, Insect Biochem. Mol. Biol., 33, 267, 10.1016/S0965-1748(02)00240-0

Munoz, 2004, Heparin-binding domains in vascular biology, Arterioscler. Thromb. Vasc. Biol., 24, 1549, 10.1161/01.ATV.0000137189.22999.3f

Nagata, 1996, Hsp47: a collagen-specific molecular chaperone, Trends Biochem. Sci., 21, 22, 10.1016/S0968-0004(06)80023-X

Nagata, 2000, Apoptotic DNA fragmentation, Exp. Cell Res., 256, 12, 10.1006/excr.2000.4834

Nakajima, 2006, A novel gene encoding a thrombin inhibitory protein in a cDNA library from Haemaphysalis longicornis salivary gland, J. Vet. Med. Sci., 68, 447, 10.1292/jvms.68.447

Narasimhan, 2013, Characterization of Ixophilin, a thrombin inhibitor from the gut of Ixodes scapularis, PLoS ONE, 8, e68012, 10.1371/journal.pone.0068012

Nurden, 2014, Platelet membrane glycoproteins: a historical review, Semin. Thromb. Hemost., 40, 577, 10.1055/s-0034-1383826

Nutt, 2002, Bax and Bak promote apoptosis by modulating endoplasmic reticular and mitochondrial Ca2+ stores, J. Biol. Chem., 277, 9219, 10.1074/jbc.M106817200

Nuttall, 2004, Tick-host interactions: saliva-activated transmission, Parasitology, 129, S177, 10.1017/S0031182004005633

Oleaga, 2015, Midgut proteome of an argasid tick, Ornithodoros erraticus: a comparison between unfed and engorged females, Parasit. Vectors, 8, 525, 10.1186/s13071-015-1148-z

Paesen, 1999, Tick histamine-binding proteins: isolation, cloning, and three-dimensional structure, Mol. Cell, 3, 661, 10.1016/S1097-2765(00)80359-7

Paesen, 2007, A tick protein with a modified Kunitz fold inhibits human tryptase, J. Mol. Biol., 368, 1172, 10.1016/j.jmb.2007.03.011

Páleníková, 2015, Ixodes ricinus salivary serpin IRS-2 affects Th17 differentiation via inhibition of the interleukin-6/STAT-3 signaling pathway, Infect. Immun., 83, 1949, 10.1128/IAI.03065-14

Payne, 2004, Mast cell tryptase: a review of its physiology and clinical significance, Anaesthesia, 59, 695, 10.1111/j.1365-2044.2004.03757.x

Pemberton, 1988, Hormone binding globulins undergo serpin conformational change in inflammation, Nature, 336, 257, 10.1038/336257a0

Peslova, 2009, Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macroglobulin in blood, Blood, 113, 6225, 10.1182/blood-2009-01-201590

Porter, 2015, Bioinformatic analyses of male and female Amblyomma americanum tick expressed serine protease inhibitors (serpins), Ticks Tick Borne Dis., 6, 16, 10.1016/j.ttbdis.2014.08.002

Prevot, 2006, Anti-hemostatic effects of a serpin from the saliva of the tick Ixodes ricinus, J. Biol. Chem., 281, 26361, 10.1074/jbc.M604197200

Prevot, 2009, Exosites mediate the anti-inflammatory effects of a multifunctional serpin from the saliva of the tick Ixodes ricinus, FEBS J., 276, 3235, 10.1111/j.1742-4658.2009.07038.x

Rachinsky, 2007, Differential protein expression in ovaries of uninfected and Babesia-infected southern cattle ticks, Rhipicephalus (Boophilus) microplus, Insect Biochem. Mol. Biol., 37, 1291, 10.1016/j.ibmb.2007.08.001

Radulovic, 2014, A 24-48 h fed Amblyomma americanum tick saliva immuno-proteome, BMC Genomics, 15, 518, 10.1186/1471-2164-15-518

Rajput, 2006, Importance of ticks and their chemical and immunological control in livestock, J. Zhejiang Univ. Sci. B, 7, 912, 10.1631/jzus.2006.B0912

Ram, 1954, On the mechanism of enzyme action. LVII. Interaction between trypsin and ovomucoid, Arch. Biochem. Biophys., 52, 451, 10.1016/0003-9861(54)90145-9

Ramamoorthi, 2005, The Lyme disease agent exploits a tick protein to infect the mammalian host, Nature, 436, 573, 10.1038/nature03812

Ranasinghe, 2013, Structure and function of invertebrate Kunitz serine protease inhibitors, Dev. Comp. Immunol., 39, 219, 10.1016/j.dci.2012.10.005

Rawlings, 2004, Evolutionary families of peptidase inhibitors, Biochem. J., 378, 705, 10.1042/bj20031825

Ray, 1992, Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme, Cell, 69, 597, 10.1016/0092-8674(92)90223-Y

Ribeiro, 1995, Blood-feeding arthropods: live syringes or invertebrate pharmacologists?, Infect. Agents Dis., 4, 143

Ribeiro, 2006, An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks, Insect Biochem. Mol. Biol., 36, 111, 10.1016/j.ibmb.2005.11.005

Ribeiro, 1985, Antihemostatic, antiinflammatory, and immunosuppressive properties of the saliva of a tick, Ixodes dammini, J. Exp. Med., 161, 332, 10.1084/jem.161.2.332

Ricci, 2007, A thrombin inhibitor from the gut of Boophilus microplus ticks, Exp. Appl. Acarol., 42, 291, 10.1007/s10493-007-9097-7

Rimphanitchayakit, 2010, Structure and function of invertebrate Kazal-type serine proteinase inhibitors, Dev. Comp. Immunol., 34, 377, 10.1016/j.dci.2009.12.004

Rodriguez-Valle, 2012, Differential recognition by tick-resistant cattle of the recombinantly expressed Rhipicephalus microplus serine protease inhibitor-3 (RMS-3), Ticks Tick Borne Dis., 3, 159, 10.1016/j.ttbdis.2012.03.002

Rodriguez-Valle, 2015, Rhipicephalus microplus serine protease inhibitor family: annotation, expression and functional characterisation assessment, Parasit. Vectors, 8, 7, 10.1186/s13071-014-0605-4

Rosario-Cruz, 2009, Genetic basis and impact of tick acaricide resistance, Front. Biosci. (Landmark Ed.), 14, 2657, 10.2741/3403

Sabbatini, 1899, Fermento anticoagulente del l'Ixodes ricinus, Ach. Ital. Biol., 31, 37

Sakai, 1996, Expression and purification of recombinant human tryptase in a baculovirus system, Protein Expr. Purif., 7, 67, 10.1006/prep.1996.0010

Sant'Anna Azzolini, 2003, Rhipicephalus sanguineus trypsin inhibitors present in the tick larvae: isolation, characterization, and partial primary structure determination, Arch. Biochem. Biophys., 417, 176, 10.1016/S0003-9861(03)00344-8

Santos, 2004, Gene discovery in Boophilus microplus, the cattle tick: the transcriptomes of ovaries, salivary glands, and hemocytes, Ann. N. Y. Acad. Sci., 1026, 242, 10.1196/annals.1307.037

Saravanan, 2003, Molecular cloning, structure and bait region splice variants of alpha2-macroglobulin from the soft tick Ornithodoros moubata, Insect Biochem. Mol. Biol., 33, 841, 10.1016/S0965-1748(03)00083-3

Sasaki, 2004, Boophilus microplus tick larvae, a rich source of Kunitz-type serine proteinase inhibitors, Biochimie, 86, 643, 10.1016/j.biochi.2004.09.010

Sasaki, 2008, BmSI-7, a novel subtilisin inhibitor from Boophilus microplus, with activity toward Pr1 proteases from the fungus Metarhizium anisopliae, Exp. Parasitol., 118, 214, 10.1016/j.exppara.2007.08.003

Sasaki, 2008, rBmTI-6, a Kunitz-BPTI domain protease inhibitor from the tick Boophilus microplus, its cloning, expression and biochemical characterization, Vet. Parasitol., 155, 133, 10.1016/j.vetpar.2008.03.031

Schlott, 2002, Interaction of Kazal-type inhibitor domains with serine proteinases: biochemical and structural studies, J. Mol. Biol., 318, 533, 10.1016/S0022-2836(02)00014-1

Schwarz, 2014, A systems level analysis reveals transcriptomic and proteomic complexity in Ixodes ricinus midgut and salivary glands during early attachment and feeding, Mol. Cell. Proteomics, 13, 2725, 10.1074/mcp.M114.039289

Soares, 2016, BmTI-A, a Kunitz-type inhibitor from Rhipicephalus microplus able to interfere in vessel formation, Vet. Parasitol., 219, 44, 10.1016/j.vetpar.2016.01.021

Soares, 2012, Expression and functional characterization of boophilin, a thrombin inhibitor from Rhipicephalus (Boophilus) microplus midgut, Vet. Parasitol., 187, 521, 10.1016/j.vetpar.2012.01.027

Somprasong, 2006, A five-domain Kazal-type serine proteinase inhibitor from black tiger shrimp Penaeus monodon and its inhibitory activities, Dev. Comp. Immun., 30, 998, 10.1016/j.dci.2006.01.004

Sonenshine, 2014, Mouthparts and digestive system, Biology of Ticks, 2nd Edn., 122

Sottrup-Jensen, 1989, Alpha-macroglobulins: structure, shape, and mechanism of proteinase complex formation, J. Biol. Chem., 264, 11539, 10.1016/S0021-9258(18)80094-1

Sottrup-Jensen, 1985, Common evolutionary origin of alpha 2-macroglobulin and complement components C3 and C4, Proc. Natl. Acad. Sci. U.S.A., 82, 9, 10.1073/pnas.82.1.9

Starkey, 1982, Evolution of alpha 2-macroglobulin. The demonstration in a variety of vertebrate species of a protein resembling human alpha 2-macroglobulin, Biochem. J., 205, 91, 10.1042/bj2050091

Stopforth, 2010, A proteomics approach for the analysis of hemolymph proteins involved in the immediate defense response of the soft tick, Ornithodoros savignyi, when challenged with Candida albicans, Exp. Appl. Acarol., 51, 309, 10.1007/s10493-010-9338-z

Sugino, 2003, A serine proteinase inhibitor (serpin) from ixodid tick Haemaphysalis longicornis; cloning and preliminary assessment of its suitability as a candidate for a tick vaccine, Vaccine, 21, 2844, 10.1016/S0264-410X(03)00167-1

Syrovets, 2012, Plasmin as a proinflammatory cell activator, J. Leukoc. Biol., 92, 509, 10.1189/jlb.0212056

Tanaka, 1999, A double headed serine proteinase inhibitor–human plasma kallikrein and elastase inhibitor–from Boophilus microplus larvae, Immunopharmacology, 45, 171, 10.1016/S0162-3109(99)00074-0

Tatchell, 1969, Host-parasite interactions and the feeding of blood-sucking arthropods, Parasitology, 59, 93, 10.1017/S0031182000069857

Tirloni, 2015, Saliva from nymph and adult females of Haemaphysalis longicornis: a proteomic study, Parasit. Vectors, 8, 338, 10.1186/s13071-015-0918-y

Tirloni, , Proteomic analysis of cattle tick Rhipicephalus (Boophilus) microplus saliva: a comparison between partially and fully engorged females, PLoS ONE, 9, e94831, 10.1371/journal.pone.0094831

Tirloni, , A family of serine protease inhibitors (serpins) in the cattle tick Rhipicephalus (Boophilus) microplus, Exp. Parasitol., 137, 25, 10.1016/j.exppara.2013.12.001

Toyomane, 2016, Identification and the preliminary in vitro characterization of IRIS homologue from salivary glands of Ixodes persulcatus Schulze, Ticks Tick Borne Dis., 7, 119, 10.1016/j.ttbdis.2015.09.006

Tsuda, 2001, cDNA cloning, characterization and vaccine effect analysis of Haemaphysalis longicornis tick saliva proteins, Vaccine, 19, 4287, 10.1016/S0264-410X(01)00148-7

Tufail, 2009, Insect vitellogenin/lipophorin receptors: molecular structures, role in oogenesis, and regulatory mechanisms, J. Insect Physiol., 55, 87, 10.1016/j.jinsphys.2008.11.007

Valdés, 2013, Tryptogalinin is a tick kunitz serine protease inhibitor with a unique intrinsic disorder, PLoS ONE, 8, e62562, 10.1371/journal.pone.0062562

van de Locht, 1996, The ornithodorin-thrombin crystal structure, a key to the TAP enigma?, EMBO J., 15, 6011, 10.1002/j.1460-2075.1996.tb00989.x

Wada, 2007, Neutrophil elastase induces cell proliferation and migration by the release of TGF-α, PDGF and VEGF in esophageal cell lines, Oncol. Rep., 17, 161, 10.3892/or.17.1.161

Walker, 1984, Effect of synthetic protease inhibitors of the amidine type on cell injury by Rickettsia rickettsii, Antimicrob. Agents Chemother., 25, 582, 10.1128/AAC.25.5.582

Wang, 2009, Characterization, kinetics, and possible function of Kazal-type proteinase inhibitors of Chinese white shrimp, Fenneropenaeus chinensis, Fish Shellfish Immunol., 26, 885, 10.1016/j.fsi.2009.03.024

Waxman, 1990, Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa, Science, 248, 593, 10.1126/science.2333510

Wikel, 2013, Ticks and tick-borne pathogens at the cutaneous interface: host defenses, tick countermeasures, and a suitable environment for pathogen establishment, Front. Microbiol., 4, 337, 10.3389/fmicb.2013.00337

Willadsen, 1980, On the biological role of a proteolytic-enzyme inhibitor from the ectoparasitic tick Boophilus microplus, Biochem. J., 189, 295, 10.1042/bj1890295

Xu, 2016, Effective inhibition of thrombin by Rhipicephalus microplus serpin-15 (RmS-15) obtained in the yeast Pichia pastoris, Ticks Tick Borne Dis., 7, 180, 10.1016/j.ttbdis.2015.09.007

Yu, 2013, Isolation and characterization of two novel serpins from the tick Rhipicephalus haemaphysaloides, Ticks Tick Borne Dis., 4, 297, 10.1016/j.ttbdis.2013.02.001

Zarbock, 2007, Platelet-neutrophil-interactions: linking hemostasis and inflammation, Blood Rev., 21, 99, 10.1016/j.blre.2006.06.001

Zhou, 2006, Identification of a follistatin-related protein from the tick Haemaphysalis longicornis and its effect on tick oviposition, Gene, 372, 191, 10.1016/j.gene.2005.12.020

Zhu, 1997, Isolation and characterization of americanin, a specific inhibitor of thrombin, from the salivary glands of the lone star tick Amblyomma americanum (L.), Exp. Parasitol., 87, 30, 10.1006/expr.1997.4175

Zou, 1994, Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells, Science, 263, 526, 10.1126/science.8290962