Macrophage-induced neutrophil apoptosis.
Macrophages (Mphi) contribute to the resolution of early inflammation by recognizing and ingesting apoptotic polymorphonuclear neutrophils (PMN). In addition, experiments reported here demonstrated that Mphi can actively induce PMN apoptosis. Coculture of cells from 2- or 5-day-old wounds in rats, or of Mphi purified from such preparations, with PMN-rich wound cell populations obtained 1 day after wounding increased PMN apoptosis by >3-fold. Neither resident- nor Proprionibacterium acnes-elicited peritoneal Mphi-induced PMN apoptosis. Apoptosis was not mediated by a soluble factor and required E:T contact. Fixed wound-Mphi and membrane isolates from viable Mphi were as effective as intact cells in inducing PMN apoptosis. Mphi-induced apoptosis was inhibited by peptide Arg-Gly-Asp-Ser, anti-beta3 (CD61) Ab, CD36 peptide, or anti-TNF-alpha Ab. Soluble TNF-alpha did not induce PMN apoptosis. In additional studies, K562 cells (negative for beta3, TNF-alpha, and Fas ligand) transfected to express either alphavbeta3 integrin, an uncleavable membrane form of TNF-alpha, or both were used in cocultures with wound PMN. Only the double transfectants were able to induce PMN apoptosis, an effect inhibited by anti-beta3 (CD61) or anti-TNF-alpha Abs. These results demonstrate that wound Mphi induce PMN apoptosis through a constitutive effector mechanism requiring both intercellular binding through integrin-ligand interactions and membrane-bound TNF-alpha.
Meszaros
A J
AJ
Department of Surgery, Rhode Island Hospital, Brown University School of Medicine, Providence, RI 02903, USA.
Reichner
J S
JS
Albina
J E
JE
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D018955:CD36 Antigens / Q000096:biosynthesis / Q000502:physiology; D002450:Cell Communication / Q000276:immunology; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018014:Gene Transfer Techniques; D006801:Humans; D039661:Integrin beta3; D020014:K562 Cells; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D019030:Receptors, Vitronectin / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D018955:CD36 Antigens; D039661:Integrin beta3; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D019030:Receptors, Vitronectin; D014409:Tumor Necrosis Factor-alpha