Macrophage-induced neutrophil apoptosis

Macrophages (M phi) contribute to the resolution of early inflammation by r ecognizing and ingesting apoptotic polymorphonuclear neutrophils (PMN). In addition, experiments reported here demonstrated that M phi can actively in duce PMN apoptosis, Coculture of cells from 2- or 5-day-old wounds in rats, or of M phi purified from such preparations, with PR M-rich wound cell pop ulations obtained 1 day after wounding increased PMN apoptosis by >3-fold. Neither resident- nor Proprionibacterium acnes-elicited peritoneal M phi-in duced PMN apoptosis, Apoptosis was not mediated by a soluble factor and req uired E:T contact. Fixed wound-M phi and membrane isolates from viable M ph i were as effective as intact cells in inducing PMN apoptosis. M phi-induce d apoptosis was inhibited by peptide Arg-Gly-Asp-Ser, anti-beta(3) (CD61) A b, CD36 peptide, or anti-TNF-alpha Ab, Soluble TNF-alpha did not induce PMN apoptosis, In additional studies, K562 cells (negative for beta(3), TNF-al pha, and Fas ligand) transfected to express either alpha(v)beta(3) integrin , an uncleavable membrane form of TNF-alpha, or both were used in coculture s with wound PMN, Only the double transfectants were able to induce PMN apo ptosis, an effect inhibited by anti-beta(3) (CD61) or anti-TNF-alpha Abs. T hese results demonstrate that wound M phi, induce PMN apoptosis through a c onstitutive effector mechanism requiring both intercellular binding through integrin-ligand interactions and membrane-bound TNF-alpha.