Abstract
Human peripheral blood monocytes are found as two distinct populations based upon differential expression of chemokine receptors, adhesion molecules, Fc receptors, and cytokines. cDNA microarray analysis now reveals additional differences between these subsets that suggest dramatically diverse functions. One monocyte subset (CD14++CD16−) appears to be closely paired with neutrophils, and may have as its primary function the removal and recycling of apoptotic neutrophils at sites of inflammation. The other monocyte subset (CD14+CD16+) expresses numerous genes encoding proteins with antimicrobial activity and thus may be more directly involved in peripheral host defense. The production of monocytes capable of efficiently removing dying neutrophils may be necessary to prevent host tissue damage and autoimmune response induction. Therefore, species like humans that produce relatively high levels of circulating neutrophils must also produce relatively high numbers of the recycling monocytes. Conversely, species such as mice and rats that maintain relatively lower levels of circulating neutrophils require fewer recycling monocytes.
Similar content being viewed by others
References
Ziegler, H. H. W. 1996. Heterogeneity of human blood monocytes: the CD14+ CD16+ subpopulation. Immunol. Today 17:424–428.
Belge, K. U., F. Dayyani, A. Horelt, M. Siedlar, M. Frankenberger, B. Frankenberger, T. Espevik, and H. L. Ziegler. 2002. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J. Immunol. 168:3536–3542.
Frankenberger, M., T. Sternsdorf, H. Pechumer, A. Pforte, and H. H. W. Ziegler. 1996. Differential cytokine expression in human blood monocyte subpopulations: a polymerase chain reaction analysis. Blood 87:373–377.
Ziegler, H. L. 2006. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J. Leukoc. Biol. 81:584–592.
Geissmann, F., S. Jung, and D. R. Littman. 2003. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82.
Potter, P. K., H. J. Cortes, P. Quartier, M. Botto, and M. J. Walport. 2003. Lupus-prone mice have an abnormal response to thioglycolate and an impaired clearance of apoptotic cells. J. Immunol. 170:3223–3232.
Sunderkötter, C., T. Nikolic, M. J. Dillon, R. N. Van, M. Stehling, D. A. Drevets, and P. J. M. Leenen. 2004. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J. Immunol. 172:4410–4417.
Gordon, S., and P. R. Taylor. 2005. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5:953–964.
Livak, K. J., and T. D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2-Delta Delta CT Method. Methods 25:402–408.
Weber, C., K. U. Belge, H. P. von, G. Draude, B. Steppich, M. Mack, M. Frankenberger, K. S. Weber, and H. H. W. Ziegler. 2000. Differential chemokine receptor expression and function in human monocyte subpopulations. J. Leukoc. Biol. 67:699–704.
Schaer, D. J., C. A. Schaer, P. W. Buehler, R. A. Boykins, G. Schoedon, A. I. Alayash, and A. Schaffner. 2006. CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin. Blood 107:373–380.
Savill, J., I. Dransfield, C. Gregory, and C. Haslett. 2002. A blast from the past: clearance of apoptotic cells regulates immune responses. Nat. Rev. Immunol. 2:965–975.
Yuita, H., M. Tsuiji, Y. Tajika, Y. Matsumoto, K. Hirano, N. Suzuki, and T. Irimura. 2005. Retardation of removal of radiation-induced apoptotic cells in developing neural tubes in macrophage galactose-type C-type lectin-1-deficient mouse embryos. Glycobiology 15:1368–1375.
Gregory, C. D., and A. Devitt. 1999. CD14 and apoptosis. Apoptosis 4:11–20.
Febbraio, M., D. P. Hajjar, and R. L. Silverstein. 2001. CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J. Clin. Invest. 108:785–791.
Dhaliwal, B. S., and U. P. Steinbrecher. 1999. Scavenger receptors and oxidized low density lipoproteins. Clin. Chim. Acta 286:191–205.
Hertzel, A. V., and D. A. Bernlohr. 2000. The mammalian fatty acid-binding protein multigene family: molecular and genetic insights into function. Trends Endocrinol. Metab. 11:175–180.
Rudel, L. L., R. G. Lee, and T. L. Cockman. 2001. Acyl coenzyme A: cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis. Curr. Opin. Lipidol. 12:121–127.
Björkhem, I., O. Andersson, U. Diczfalusy, B. Sevastik, R. J. Xiu, C. Duan, and E. Lund. 1994. Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages. Proc. Natl. Acad. Sci. USA 91:8592–8596.
Bowdish, D. M. E., D. J. Davidson, and R. E. W. Hancock. 2006. Immunomodulatory properties of defensins and cathelicidins. Curr. Top. Microbiol. Immunol. 306:27–66.
Kishore, U., T. J. Greenhough, P. Waters, A. K. Shrive, R. Ghai, M. F. Kamran, A. L. Bernal, K. B. M. Reid, T. Madan, and T. Chakraborty. 2006. Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol. Immunol. 43:1293–1315.
Sim, R. B., H. Clark, K. Hajela, and K. R. Mayilyan. 2006. Collectins and host defence. Novartis Found. Symp. 279:170–181.
Berdowska, I. 2004. Cysteine proteases as disease markers. Clin. Chim. Acta 342:41–69.
Dollery, C. M., C. A. Owen, G. K. Sukhova, A. Krettek, S. D. Shapiro, and P. Libby. 2003. Neutrophil elastase in human atherosclerotic plaques: production by macrophages. Circulation 107:2829–2836.
Flo, T. H., K. D. Smith, S. Sato, D. J. Rodriguez, M. A. Holmes, R. K. Strong, S. Akira, and A. Aderem. 2004. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432:917–921.
Lambert, L. A., H. Perri, and T. J. Meehan. 2005. Evolution of duplications in the transferrin family of proteins. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 140:11–25.
Tracey, K. J., and A. Cerami. 1994. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu. Rev. Med. 45:491–503.
Leizer, T., J. Cebon, J. E. Layton, and J. A. Hamilton. 1990. Cytokine regulation of colony-stimulating factor production in cultured human synovial fibroblasts: I Induction of GM-CSF and G-CSF production by interleukin-1 and tumor necrosis factor. Blood 76:1989–1996.
Saleh, M. N., S. J. Goldman, A. F. LoBuglio, A. C. Beall, H. Sabio, M. C. McCord, L. Minasian, R. K. Alpaugh, L. M. Weiner, and D. H. Munn. 1995. CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony-stimulating factor. Blood 85:2910–2917.
Witmer, P. M. D., D. A. Hughes, G. Schuler, L. Lawson, A. McWilliam, K. Inaba, R. M. Steinman, and S. Gordon. 1993. Identification of macrophages and dendritic cells in the osteopetrotic op/op mouse. J. Cell Sci. 104:1021–1029.
Beutler, E., M. A. Lichtman, B. S. Coller, and T. J. Kipps eds. 1995. Williams Hematology. McGraw-Hill, Inc., New York.
Feldman, B. F., J. G. Zinkl, and N. C. Jain eds. 2000. Schalm’s Veterinary Hematology. Lippincott Williams & Wilkins, Philadelphia.
Read, A. F., and J. E. Allen. 2000. Evolution and immunology: The economics of immunity. Science 290:1104–1105.
Nunn, C. L., J. L. Gittleman, and J. Antonovics. 2000. Promiscuity and the primate immune system. Science 290:1168–1170.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mobley, J.L., Leininger, M., Madore, S. et al. Genetic Evidence of a Functional Monocyte Dichotomy. Inflammation 30, 189–197 (2007). https://doi.org/10.1007/s10753-007-9036-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-007-9036-0