Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 Mar 1;179(3):1047–1052. doi: 10.1084/jem.179.3.1047

bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages

PMCID: PMC2191411  PMID: 8113673

Abstract

Neutrophils, the most common inflammatory leukocytes, have the most limited life span of all blood cells. After they undergo apoptosis, they are recognized and engulfed by macrophages. bcl-2, a proto- oncogene rearranged and deregulated in B cell lymphomas bearing the t(14;18) translocation, is known to inhibit programmed death. bcl-2 expression is localized in early myeloid cells of the bone marrow but is absent in mature neutrophils. Transgenic mice that expressed bcl-2 in mature neutrophils showed that bcl-2 blocked neutrophil apoptosis. Despite this, homeostasis of neutrophil population is essentially unaffected. In fact, macrophage uptake of neutrophils expressing bcl-2 still occurred. This transgenic model indicates that the mechanism that triggers phagocytosis of aging neutrophils operates independently of the process of apoptosis regulated by bcl-2.

Full Text

The Full Text of this article is available as a PDF (984.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cleary M. L., Sklar J. Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7439–7443. doi: 10.1073/pnas.82.21.7439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cochrane C. G. Immunologic tissue injury mediated by neutrophilic leukocytes. Adv Immunol. 1968;9:97–162. doi: 10.1016/s0065-2776(08)60442-3. [DOI] [PubMed] [Google Scholar]
  3. Delia D., Aiello A., Soligo D., Fontanella E., Melani C., Pezzella F., Pierotti M. A., Della Porta G. bcl-2 proto-oncogene expression in normal and neoplastic human myeloid cells. Blood. 1992 Mar 1;79(5):1291–1298. [PubMed] [Google Scholar]
  4. Desaga J. F., Parwaresch M. R. Zur intravasalen Kinetik der neutrophilen Granulocyten des Kaninchens. Klin Wochenschr. 1972 Aug 15;50(16):795–796. doi: 10.1007/BF01490311. [DOI] [PubMed] [Google Scholar]
  5. Driscoll M. Molecular genetics of cell death in the nematode Caenorhabditis elegans. J Neurobiol. 1992 Nov;23(9):1327–1351. doi: 10.1002/neu.480230919. [DOI] [PubMed] [Google Scholar]
  6. Ellis H. M., Horvitz H. R. Genetic control of programmed cell death in the nematode C. elegans. Cell. 1986 Mar 28;44(6):817–829. doi: 10.1016/0092-8674(86)90004-8. [DOI] [PubMed] [Google Scholar]
  7. Ellis R. E., Jacobson D. M., Horvitz H. R. Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans. Genetics. 1991 Sep;129(1):79–94. doi: 10.1093/genetics/129.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fadok V. A., Savill J. S., Haslett C., Bratton D. L., Doherty D. E., Campbell P. A., Henson P. M. Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J Immunol. 1992 Dec 15;149(12):4029–4035. [PubMed] [Google Scholar]
  9. Grigg J. M., Savill J. S., Sarraf C., Haslett C., Silverman M. Neutrophil apoptosis and clearance from neonatal lungs. Lancet. 1991 Sep 21;338(8769):720–722. doi: 10.1016/0140-6736(91)91443-x. [DOI] [PubMed] [Google Scholar]
  10. Hengartner M. O., Ellis R. E., Horvitz H. R. Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature. 1992 Apr 9;356(6369):494–499. doi: 10.1038/356494a0. [DOI] [PubMed] [Google Scholar]
  11. Hockenbery D. M., Zutter M., Hickey W., Nahm M., Korsmeyer S. J. BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6961–6965. doi: 10.1073/pnas.88.16.6961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Inaba M., Inaba K., Hosono M., Kumamoto T., Ishida T., Muramatsu S., Masuda T., Ikehara S. Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells. J Exp Med. 1991 Mar 1;173(3):549–559. doi: 10.1084/jem.173.3.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jones S. T., Denton J., Holt P. J., Freemont A. J. Possible clearance of effete polymorphonuclear leucocytes from synovial fluid by cytophagocytic mononuclear cells: implications for pathogenesis and chronicity in inflammatory arthritis. Ann Rheum Dis. 1993 Feb;52(2):121–126. doi: 10.1136/ard.52.2.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lagasse E., Clerc R. G. Cloning and expression of two human genes encoding calcium-binding proteins that are regulated during myeloid differentiation. Mol Cell Biol. 1988 Jun;8(6):2402–2410. doi: 10.1128/mcb.8.6.2402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lagasse E., Weissman I. L. Mouse MRP8 and MRP14, two intracellular calcium-binding proteins associated with the development of the myeloid lineage. Blood. 1992 Apr 15;79(8):1907–1915. [PubMed] [Google Scholar]
  16. Lancaster M. G., Allison F., Jr Studies on the pathogenesis of acute inflammation. VII. The influence of osmolality upon the phagocytic and clumping activity by human leukocytes. Am J Pathol. 1966 Dec;49(6):1185–1200. [PMC free article] [PubMed] [Google Scholar]
  17. Leibovich S. J., Ross R. The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol. 1975 Jan;78(1):71–100. [PMC free article] [PubMed] [Google Scholar]
  18. Mazda O., Watanabe Y., Gyotoku J., Katsura Y. Requirement of dendritic cells and B cells in the clonal deletion of Mls-reactive T cells in the thymus. J Exp Med. 1991 Mar 1;173(3):539–547. doi: 10.1084/jem.173.3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Newman S. L., Henson J. E., Henson P. M. Phagocytosis of senescent neutrophils by human monocyte-derived macrophages and rabbit inflammatory macrophages. J Exp Med. 1982 Aug 1;156(2):430–442. doi: 10.1084/jem.156.2.430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rothenberg E. V. The development of functionally responsive T cells. Adv Immunol. 1992;51:85–214. doi: 10.1016/s0065-2776(08)60487-3. [DOI] [PubMed] [Google Scholar]
  21. Sanui H., Yoshida S., Nomoto K., Ohhara R., Adachi Y. Peritoneal macrophages which phagocytose autologous polymorphonuclear leucocytes in guinea-pigs. I: induction by irritants and microorgansisms and inhibition by colchicine. Br J Exp Pathol. 1982 Jun;63(3):278–284. [PMC free article] [PubMed] [Google Scholar]
  22. Savill J. S., Wyllie A. H., Henson J. E., Walport M. J., Henson P. M., Haslett C. Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. J Clin Invest. 1989 Mar;83(3):865–875. doi: 10.1172/JCI113970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Savill J., Fadok V., Henson P., Haslett C. Phagocyte recognition of cells undergoing apoptosis. Immunol Today. 1993 Mar;14(3):131–136. doi: 10.1016/0167-5699(93)90215-7. [DOI] [PubMed] [Google Scholar]
  24. Savill J. Macrophage recognition of senescent neutrophils. Clin Sci (Lond) 1992 Dec;83(6):649–655. doi: 10.1042/cs0830649. [DOI] [PubMed] [Google Scholar]
  25. Sentman C. L., Shutter J. R., Hockenbery D., Kanagawa O., Korsmeyer S. J. bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell. 1991 Nov 29;67(5):879–888. doi: 10.1016/0092-8674(91)90361-2. [DOI] [PubMed] [Google Scholar]
  26. Shortman K., Vremec D. Different subpopulations of developing thymocytes are associated with adherent (macrophage) or nonadherent (dendritic) thymic rosettes. Dev Immunol. 1991;1(3):225–235. doi: 10.1155/1991/49025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tsujimoto Y., Gorham J., Cossman J., Jaffe E., Croce C. M. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985 Sep 27;229(4720):1390–1393. doi: 10.1126/science.3929382. [DOI] [PubMed] [Google Scholar]
  28. Vaux D. L., Cory S., Adams J. M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 1988 Sep 29;335(6189):440–442. doi: 10.1038/335440a0. [DOI] [PubMed] [Google Scholar]
  29. Vaux D. L., Weissman I. L., Kim S. K. Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science. 1992 Dec 18;258(5090):1955–1957. doi: 10.1126/science.1470921. [DOI] [PubMed] [Google Scholar]
  30. Whyte M. K., Meagher L. C., MacDermot J., Haslett C. Impairment of function in aging neutrophils is associated with apoptosis. J Immunol. 1993 Jun 1;150(11):5124–5134. [PubMed] [Google Scholar]
  31. Willoughby D. A., Giroud J. P. The role of polymorphonuclear leucocytes in acute inflammation in agranulocytic rats. J Pathol. 1969 May;98(1):53–60. doi: 10.1002/path.1710980107. [DOI] [PubMed] [Google Scholar]
  32. Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES