Identification of an Autophagy Defect in Smokers’ Alveolar Macrophages
Tóm tắt
Alveolar macrophages are essential for clearing bacteria from the alveolar surface and preventing microbe-induced infections. It is well documented that smokers have an increased incidence of infections, in particular lung infections. Alveolar macrophages accumulate in smokers’ lungs, but they have a functional immune deficit. In this study, we identify an autophagy defect in smokers’ alveolar macrophages. Smokers’ alveolar macrophages accumulate both autophagosomes and p62, a marker of autophagic flux. The decrease in the process of autophagy leads to impaired protein aggregate clearance, dysfunctional mitochondria, and defective delivery of bacteria to lysosomes. This study identifies the autophagy pathway as a potential target for interventions designed to decrease infection rates in smokers and possibly in individuals with high environmental particulate exposure.
Từ khóa
Tài liệu tham khảo
Niewoehner, 1974, Pathologic changes in the peripheral airways of young cigarette smokers., N. Engl. J. Med., 291, 755, 10.1056/NEJM197410102911503
Green, 1968, Cigarette smoke: protection of alveolar macrophages by glutathione and cysteine., Science, 162, 810, 10.1126/science.162.3855.810
Laurenzi, 1963, Clearance of bacteria by the lower respiratory tract., Science, 142, 1572, 10.1126/science.142.3599.1572
Klionsky, 2000, Autophagy as a regulated pathway of cellular degradation., Science, 290, 1717, 10.1126/science.290.5497.1717
Mizushima, 2008, Autophagy fights disease through cellular self-digestion., Nature, 451, 1069, 10.1038/nature06639
Travassos, 2010, Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry., Nat. Immunol., 11, 55, 10.1038/ni.1823
Chen, 2008, Egr-1 regulates autophagy in cigarette smoke-induced chronic obstructive pulmonary disease., PLoS One, 3, e3316, 10.1371/journal.pone.0003316
Kim, 2008, Autophagic proteins regulate cigarette smoke-induced apoptosis: protective role of heme oxygenase-1., Autophagy, 4, 887, 10.4161/auto.6767
Nuorti, 2000, Cigarette smoking and invasive pneumococcal disease., N. Engl. J. Med., 342, 681, 10.1056/NEJM200003093421002
Drannik, 2004, Impact of cigarette smoke on clearance and inflammation after Pseudomonas aeruginosa infection., Am. J. Respir. Crit. Care Med., 170, 1164, 10.1164/rccm.200311-1521OC
Ju, 2009, Quantitation of selective autophagic protein aggregate degradation in vitro and in vivo using luciferase reporters., Autophagy, 5, 511, 10.4161/auto.5.4.7761
Monick, 1999, Human alveolar macrophages are markedly deficient in REF-1 and AP-1 DNA binding activity., J. Biol. Chem., 274, 18075, 10.1074/jbc.274.25.18075
Nyunoya, 2006, Cigarette smoke induces cellular senescence., Am. J. Respir. Cell Mol. Biol., 35, 681, 10.1165/rcmb.2006-0169OC
Nyunoya, 2009, Cigarette smoke induces cellular senescence via Werner’s syndrome protein down-regulation., Am. J. Respir. Crit. Care Med., 179, 279, 10.1164/rccm.200802-320OC
Blue, 1978, Possible mechanisms of emphysema in cigarette smokers. Release of elastase from human polymorphonuclear leukocytes by cigarette smoke condensate in vitro., Am. Rev. Respir. Dis., 117, 317
Panayiotidis, 2004, Cigarette smoke extract increases S-adenosylmethionine and cystathionine in human lung epithelial-like (A549) cells., Chem. Biol. Interact., 147, 87, 10.1016/j.cbi.2003.10.009
Carnevali, 2003, Cigarette smoke extract induces oxidative stress and apoptosis in human lung fibroblasts., Am. J. Physiol. Lung Cell. Mol. Physiol., 284, L955, 10.1152/ajplung.00466.2001
Hansdottir, 2008, Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense., J. Immunol., 181, 7090, 10.4049/jimmunol.181.10.7090
Monick, 2008, Constitutive ERK MAPK activity regulates macrophage ATP production and mitochondrial integrity., J. Immunol., 180, 7485, 10.4049/jimmunol.180.11.7485
Klionsky, 2008, Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes., Autophagy, 4, 151, 10.4161/auto.5338
Mizushima, 2010, Methods in mammalian autophagy research., Cell, 140, 313, 10.1016/j.cell.2010.01.028
Ding, 2010, Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice., Gastroenterology, 10.1053/j.gastro.2010.07.041
Ogier-Denis, 1996, Guanine nucleotide exchange on heterotrimeric Gi3 protein controls autophagic sequestration in HT-29 cells., J. Biol. Chem., 271, 28593, 10.1074/jbc.271.45.28593
Komatsu, 2010, The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1., Nat. Cell Biol., 12, 213, 10.1038/ncb2021
Moscat, 2009, To aggregate or not to aggregate? A new role for p62., EMBO Rep., 10, 804, 10.1038/embor.2009.172
Moscat, 2009, p62 at the crossroads of autophagy, apoptosis, and cancer., Cell, 137, 1001, 10.1016/j.cell.2009.05.023
Ponpuak, 2010, Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties., Immunity, 32, 329, 10.1016/j.immuni.2010.02.009
Kirkin, 2009, A role for ubiquitin in selective autophagy., Mol. Cell, 34, 259, 10.1016/j.molcel.2009.04.026
Moscat, 2006, Cell signaling and function organized by PB1 domain interactions., Mol. Cell, 23, 631, 10.1016/j.molcel.2006.08.002
Pankiv, 2007, p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy., J. Biol. Chem., 282, 24131, 10.1074/jbc.M702824200
Kim, 2008, Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes., Proc. Natl. Acad. Sci. USA, 105, 20567, 10.1073/pnas.0810611105
Olzmann, 2007, Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6., J. Cell Biol., 178, 1025, 10.1083/jcb.200611128
Tan, 2008, Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases., Hum. Mol. Genet., 17, 431, 10.1093/hmg/ddm320
Wooten, 2008, Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins., J. Biol. Chem., 283, 6783, 10.1074/jbc.M709496200
Hemelaar, 2004, Specific and covalent targeting of conjugating and deconjugating enzymes of ubiquitin-like proteins., Mol. Cell. Biol., 24, 84, 10.1128/MCB.24.1.84-95.2004
Hochstrasser, 2000, Biochemistry. All in the ubiquitin family., Science, 289, 563, 10.1126/science.289.5479.563
Hochstrasser, 2000, Evolution and function of ubiquitin-like protein-conjugation systems., Nat. Cell Biol., 2, E153, 10.1038/35019643
Ulrich, 2008, The fast-growing business of SUMO chains., Mol. Cell, 32, 301, 10.1016/j.molcel.2008.10.010
Mathew, 2009, Autophagy suppresses tumorigenesis through elimination of p62., Cell, 137, 1062, 10.1016/j.cell.2009.03.048
Kanki, 2008, Mitophagy in yeast occurs through a selective mechanism., J. Biol. Chem., 283, 32386, 10.1074/jbc.M802403200
Deretic, 2009, Autophagy, immunity, and microbial adaptations., Cell Host Microbe, 5, 527, 10.1016/j.chom.2009.05.016
Gutierrez, 2004, Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages., Cell, 119, 753, 10.1016/j.cell.2004.11.038
Levine, 2005, Eating oneself and uninvited guests: autophagy-related pathways in cellular defense., Cell, 120, 159
Jia, 2009, Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance., Proc. Natl. Acad. Sci. USA, 106, 14564, 10.1073/pnas.0813319106
Qu, 2007, Autophagy gene-dependent clearance of apoptotic cells during embryonic development., Cell, 128, 931, 10.1016/j.cell.2006.12.044
Montgomery, 1991, Accumulation of indigestible substances reduces fusion competence of macrophage lysosomes., J. Immunol., 147, 3087, 10.4049/jimmunol.147.9.3087
Korolchuk, 2009, Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates., Mol. Cell, 33, 517, 10.1016/j.molcel.2009.01.021
Ivanov, 2009, NDP52: the missing link between ubiquitinated bacteria and autophagy., Nat. Immunol., 10, 1137, 10.1038/ni1109-1137
Elmore, 2001, The mitochondrial permeability transition initiates autophagy in rat hepatocytes., FASEB J., 15, 2286, 10.1096/fj.01-0206fje
Kim, 2007, Selective degradation of mitochondria by mitophagy., Arch. Biochem. Biophys., 462, 245, 10.1016/j.abb.2007.03.034
Narendra, 2008, Parkin is recruited selectively to impaired mitochondria and promotes their autophagy., J. Cell Biol., 183, 795, 10.1083/jcb.200809125
Vives-Bauza, 2010, PINK1-dependent recruitment of Parkin to mitochondria in mitophagy., Proc. Natl. Acad. Sci. USA, 107, 378, 10.1073/pnas.0911187107
Novak, 2010, Nix is a selective autophagy receptor for mitochondrial clearance., EMBO Rep., 11, 45, 10.1038/embor.2009.256
Yoshikawa, 2009, Listeria monocytogenes ActA-mediated escape from autophagic recognition., Nat. Cell Biol., 11, 1233, 10.1038/ncb1967
Zheng, 2009, The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway., J. Immunol., 183, 5909, 10.4049/jimmunol.0900441