title: Macrophages induce neutrophil apoptosis through membrane TNF, a process amplified by Leishmania major.
abstract: Neutrophils are recruited to the site of parasite inoculation within a few hours of infection with the protozoan parasite Leishmania major. In C57BL/6 mice, which are resistant to infection, neutrophils are cleared from the site of s.c. infection within 3 days, whereas they persist for at least 10 days in susceptible BALB/c mice. In the present study, we investigated the role of macrophages (MPhi) in regulating neutrophil number. Inflammatory cells were recruited by i.p. injection of either 2% starch or L. major promastigotes. Neutrophils were isolated and cultured in the presence of increasing numbers of MPhi. Extent of neutrophil apoptosis positively correlated with the number of MPhi added. This process was strictly dependent on TNF because MPhi from TNF-deficient mice failed to induce neutrophil apoptosis. Assays using MPhi derived from membrane TNF knock-in mice or cultures in Transwell chambers revealed that contact with MPhi was necessary to induce neutrophil apoptosis, a process requiring expression of membrane TNF. L. major was shown to exacerbate MPhi-induced apoptosis of neutrophils, but BALB/c MPhi were not as potent as C57BL/6 MPhi in this induction. Our results emphasize the importance of MPhi-induced neutrophil apoptosis, and membrane TNF in the early control of inflammation.
authors.affiliation: World Health Organization (WHO) Immunology Research and Training Center, Department of Biochemistry, Epalinges, Switzerland.
authors.forename: Cindy
authors.initials: C
authors.lastname: Allenbach
authors.forename: Christel
authors.initials: C
authors.lastname: Zufferey
authors.forename: Cynthia
authors.initials: C
authors.lastname: Perez
authors.forename: Pascal
authors.initials: P
authors.lastname: Launois
authors.forename: Christoph
authors.initials: C
authors.lastname: Mueller
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tacchini-Cottier
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D018320:Leishmania major / Q000276:immunology*; D007958:Leukocyte Count; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D013045:Species Specificity; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha