Inflammation

, Volume 30, Issue 6, pp 189–197 | Cite as

Genetic Evidence of a Functional Monocyte Dichotomy

  • James L. Mobley
  • Michael Leininger
  • Steven Madore
  • Theodore J. Baginski
  • Richard Renkiewicz
Article

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.

Key words

monocytes macrophages differentiation inflammation differential display 

References

  1. 1.
    Ziegler, H. H. W. 1996. Heterogeneity of human blood monocytes: the CD14+ CD16+ subpopulation. Immunol. Today 17:424–428.CrossRefGoogle Scholar
  2. 2.
    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.PubMedGoogle Scholar
  3. 3.
    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.PubMedGoogle Scholar
  4. 4.
    Ziegler, H. L. 2006. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J. Leukoc. Biol. 81:584–592.CrossRefGoogle Scholar
  5. 5.
    Geissmann, F., S. Jung, and D. R. Littman. 2003. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82.PubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedGoogle Scholar
  7. 7.
    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.PubMedGoogle Scholar
  8. 8.
    Gordon, S., and P. R. Taylor. 2005. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5:953–964.PubMedCrossRefGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    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.PubMedGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    Gregory, C. D., and A. Devitt. 1999. CD14 and apoptosis. Apoptosis 4:11–20.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    Dhaliwal, B. S., and U. P. Steinbrecher. 1999. Scavenger receptors and oxidized low density lipoproteins. Clin. Chim. Acta 286:191–205.PubMedCrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCrossRefGoogle Scholar
  20. 20.
    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.PubMedGoogle Scholar
  21. 21.
    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.PubMedCrossRefGoogle Scholar
  22. 22.
    Sim, R. B., H. Clark, K. Hajela, and K. R. Mayilyan. 2006. Collectins and host defence. Novartis Found. Symp. 279:170–181.PubMedCrossRefGoogle Scholar
  23. 23.
    Berdowska, I. 2004. Cysteine proteases as disease markers. Clin. Chim. Acta 342:41–69.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCrossRefGoogle Scholar
  27. 27.
    Tracey, K. J., and A. Cerami. 1994. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu. Rev. Med. 45:491–503.PubMedCrossRefGoogle Scholar
  28. 28.
    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.PubMedGoogle Scholar
  29. 29.
    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.PubMedGoogle Scholar
  30. 30.
    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.Google Scholar
  31. 31.
    Beutler, E., M. A. Lichtman, B. S. Coller, and T. J. Kipps eds. 1995. Williams Hematology. McGraw-Hill, Inc., New York.Google Scholar
  32. 32.
    Feldman, B. F., J. G. Zinkl, and N. C. Jain eds. 2000. Schalm’s Veterinary Hematology. Lippincott Williams & Wilkins, Philadelphia.Google Scholar
  33. 33.
    Read, A. F., and J. E. Allen. 2000. Evolution and immunology: The economics of immunity. Science 290:1104–1105.PubMedCrossRefGoogle Scholar
  34. 34.
    Nunn, C. L., J. L. Gittleman, and J. Antonovics. 2000. Promiscuity and the primate immune system. Science 290:1168–1170.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • James L. Mobley
    • 1
  • Michael Leininger
    • 1
  • Steven Madore
    • 1
  • Theodore J. Baginski
    • 1
  • Richard Renkiewicz
    • 1
  1. 1.Pfizer Global Research and DevelopmentAnn ArborUSA

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