Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults

BMC Immunology - Tập 11 Số 1 - 2010
Sebastian Seidler1, Henning W. Zimmermann1, Matthias Bartneck2, Christian Trautwein1, Frank Tacke1
1Department of Medicine III, University Hospital, RWTH-Aachen, Pauwelsstr 30, 52074, Aachen, Germany
2Interdisciplinary Centre for Clinical Research, University Hospital, RWTH-Aachen, Pauwelsstr 30, 52074, Aachen, Germany

Tóm tắt

Abstract Background Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during ageing, potentially influencing their functionality and contributing to immunosenescence. Results Circulating monocyte subsets, surface marker and chemokine receptor expression were analyzed in 181 healthy volunteers (median age 42, range 18-88). Unlike the unaffected total leukocyte or total monocyte counts, non-classical CD14+CD16+ monocytes significantly increased with age, but displayed reduced HLA-DR and CX3CR1 surface expression in the elderly. Classical CD14++CD16- monocyte counts did not vary dependent on age. Serum MCP-1 (CCL2), but not MIP1α (CCL3), MIP1β (CCL4) or fractalkine (CX3CL1) concentrations increased with age. Monocyte-derived macrophages from old or young individuals did not differ with respect to cytokine release in vitro at steady state or upon LPS stimulation. Conclusions Our study demonstrates dynamic changes of circulating monocytes during ageing in humans. The expansion of the non-classical CD14+CD16+ subtype, alterations of surface protein and chemokine receptor expression as well as circulating monocyte-related chemokines possibly contribute to the preserved functionality of the monocyte pool throughout adulthood.

Từ khóa


Tài liệu tham khảo

Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K: Development of monocytes, macrophages, and dendritic cells. Science. 2010, 327: 656-61. 10.1126/science.1178331.

Tacke F, Randolph GJ: Migratory fate and differentiation of blood monocyte subsets. Immunobiology. 2006, 211: 609-18. 10.1016/j.imbio.2006.05.025.

Geissmann F, Jung S, Littman DR: Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity. 2003, 19: 71-82. 10.1016/S1074-7613(03)00174-2.

Raff HV, Picker LJ, Stobo JD: Macrophage heterogeneity in man. A subpopulation of HLA-DR-bearing macrophages required for antigen-induced T cell activation also contains stimulators for autologous-reactive T cells. J Exp Med. 1980, 152: 581-93. 10.1084/jem.152.3.581.

Arenson EB, Epstein MB, Seeger RC: Volumetric and functional heterogeneity of human monocytes. J Clin Invest. 1980, 65: 613-8. 10.1172/JCI109706.

Grage-Griebenow E, Lorenzen D, Fetting R, Flad HD, Ernst M: Phenotypical and functional characterization of Fc gamma receptor I (CD64)-negative monocytes, a minor human monocyte subpopulation with high accessory and antiviral activity. Eur J Immunol. 1993, 23: 3126-35. 10.1002/eji.1830231213.

Passlick B, Flieger D, Ziegler-Heitbrock HW: Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood. 1989, 74: 2527-34.

Ingersoll MA, Spanbroek R, Lottaz C, Gautier EL, Frankenberger M, Hoffmann R, Lang R, Haniffa M, Collin M, Tacke F, et al.,: Comparison of gene expression profiles between human and mouse monocyte subsets. Blood. 2010, 115: e10-9. 10.1182/blood-2009-07-235028.

Karlmark KR, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, Merad M, Luedde T, Trautwein C, Tacke F: Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology. 2009, 50: 261-74. 10.1002/hep.22950.

Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, Llodra J, Garin A, Liu J, Mack M, van Rooijen N, et al.,: Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest. 2007, 117: 185-94. 10.1172/JCI28549.

Auffray C, Sieweke MH, Geissmann F: Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 2009, 27: 669-92. 10.1146/annurev.immunol.021908.132557.

Tacke F, Luedde T, Trautwein C: Inflammatory pathways in liver homeostasis and liver injury. Clin Rev Allergy Immunol. 2009, 36: 4-12. 10.1007/s12016-008-8091-0.

Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, Sarnacki S, Cumano A, Lauvau G, Geissmann F: Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science. 2007, 317: 666-70. 10.1126/science.1142883.

Serbina NV, Pamer EG: Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol. 2006, 7: 311-7. 10.1038/ni1309.

Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ: The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007, 204: 3037-47. 10.1084/jem.20070885.

Sadeghi HM, Schnelle JF, Thoma JK, Nishanian P, Fahey JL: Phenotypic and functional characteristics of circulating monocytes of elderly persons. Exp Gerontol. 1999, 34: 959-70. 10.1016/S0531-5565(99)00065-0.

Ligthart GJ, Corberand JX, Fournier C, Galanaud P, Hijmans W, Kennes B, Muller-Hermelink HK, Steinmann GG: Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev. 1984, 28: 47-55. 10.1016/0047-6374(84)90152-0.

Castle SC, Uyemura K, Makinodan T: The SENIEUR Protocol after 16 years: a need for a paradigm shift?. Mech Ageing Dev. 2001, 122: 127-30. 10.1016/S0047-6374(00)00238-4.

Zimmermann HW, Seidler S, Nattermann J, Gassler N, Hellerbrand C, Zernecke A, Tischendorf JJW, Luedde T, Weiskirchen R, Trautwein C, et al.,: Functional contribution of elevated circulating and hepatic non-classical CD14+CD16+ monocytes to inflammation and human liver fibrosis. PLoS One. 2010, 5: e11049-10.1371/journal.pone.0011049.

Yagmur E, Weiskirchen R, Gressner AM, Trautwein C, Tacke F: Insulin resistance in liver cirrhosis is not associated with circulating retinol-binding protein 4. Diabetes Care. 2007, 30: 1168-72. 10.2337/dc06-2323.

Lukacs-Kornek V, Engel D, Tacke F, Kurts C: The role of chemokines and their receptors in dendritic cell biology. Front Biosci. 2008, 13: 2238-52. 10.2741/2838.

Tsou CL, Peters W, Y Si, Slaymaker S, Aslanian AM, Weisberg SP, Mack M, Charo IF: Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest. 2007, 117: 902-9. 10.1172/JCI29919.

Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P, et al.,: Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science. 2009, 325: 612-6. 10.1126/science.1175202.

Jakubzick C, Tacke F, Ginhoux F, Wagers AJ, van Rooijen N, Mack M, Merad M, Randolph GJ: Blood monocyte subsets differentially give rise to CD103+ and CD103- pulmonary dendritic cell populations. J Immunol. 2008, 180: 3019-27.

McElhaney JE, Effros RB: Immunosenescence: what does it mean to health outcomes in older adults?. Curr Opin Immunol. 2009, 21: 418-24. 10.1016/j.coi.2009.05.023.

Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC: Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol. 2009, 30: 325-33. 10.1016/j.it.2009.05.004.

Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R, Shagdarsuren E, Lira SA, Weissman IL, Weber C, Jung S: CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood. 2009, 113: 963-72. 10.1182/blood-2008-07-170787.

Auffray C, Fogg DK, Narni-Mancinelli E, Senechal B, Trouillet C, Saederup N, Leemput J, Bigot K, Campisi L, Abitbol M, et al.,: CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation. J Exp Med. 2009, 206: 595-606. 10.1084/jem.20081385.

Gautier EL, Jakubzick C, Randolph GJ: Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis. Arterioscler Thromb Vasc Biol. 2009, 29: 1412-8. 10.1161/ATVBAHA.108.180505.

Inadera H, Egashira K, Takemoto M, Ouchi Y, Matsushima K: Increase in circulating levels of monocyte chemoattractant protein-1 with aging. J Interferon Cytokine Res. 1999, 19: 1179-82. 10.1089/107999099313127.

Antonelli A, Rotondi M, Fallahi P, Ferrari SM, Paolicchi A, Romagnani P, Serio M, Ferrannini E: Increase of CXC chemokine CXCL10 and CC chemokine CCL2 serum levels in normal ageing. Cytokine. 2006, 34: 32-8. 10.1016/j.cyto.2006.03.012.

Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, et al.,: MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006, 116: 1494-505. 10.1172/JCI26498.

Obstfeld AE, Sugaru E, Thearle M, Francisco AM, Gayet C, Ginsberg HN, Ables EV, Ferrante AW: C-C chemokine receptor 2 (CCR2) regulates the hepatic recruitment of myeloid cells that promote obesity-induced hepatic steatosis. Diabetes. 2010, 59: 916-25. 10.2337/db09-1403.

Ahluwalia N, Mastro AM, Ball R, Miles MP, Rajendra R, Handte G: Cytokine production by stimulated mononuclear cells did not change with aging in apparently healthy, well-nourished women. Mech Ageing Dev. 2001, 122: 1269-79. 10.1016/S0047-6374(01)00266-4.

Fagiolo U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Monti D, Franceschi C, Paganelli R: Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol. 1993, 23: 2375-8. 10.1002/eji.1830230950.