Skip to main content
Log in

Genetic Evidence of a Functional Monocyte Dichotomy

  • Published:
Inflammation Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ziegler, H. H. W. 1996. Heterogeneity of human blood monocytes: the CD14+ CD16+ subpopulation. Immunol. Today 17:424–428.

    Article  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  4. Ziegler, H. L. 2006. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J. Leukoc. Biol. 81:584–592.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  8. Gordon, S., and P. R. Taylor. 2005. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5:953–964.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  14. Gregory, C. D., and A. Devitt. 1999. CD14 and apoptosis. Apoptosis 4:11–20.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  16. Dhaliwal, B. S., and U. P. Steinbrecher. 1999. Scavenger receptors and oxidized low density lipoproteins. Clin. Chim. Acta 286:191–205.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  22. Sim, R. B., H. Clark, K. Hajela, and K. R. Mayilyan. 2006. Collectins and host defence. Novartis Found. Symp. 279:170–181.

    Article  PubMed  CAS  Google Scholar 

  23. Berdowska, I. 2004. Cysteine proteases as disease markers. Clin. Chim. Acta 342:41–69.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  27. Tracey, K. J., and A. Cerami. 1994. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu. Rev. Med. 45:491–503.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. Beutler, E., M. A. Lichtman, B. S. Coller, and T. J. Kipps eds. 1995. Williams Hematology. McGraw-Hill, Inc., New York.

    Google Scholar 

  32. Feldman, B. F., J. G. Zinkl, and N. C. Jain eds. 2000. Schalm’s Veterinary Hematology. Lippincott Williams & Wilkins, Philadelphia.

    Google Scholar 

  33. Read, A. F., and J. E. Allen. 2000. Evolution and immunology: The economics of immunity. Science 290:1104–1105.

    Article  PubMed  CAS  Google Scholar 

  34. Nunn, C. L., J. L. Gittleman, and J. Antonovics. 2000. Promiscuity and the primate immune system. Science 290:1168–1170.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to James L. Mobley.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-007-9036-0

Key words

Navigation