title: Cross-linking of human FcgammaRIIIb induces the production of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor by polymorphonuclear neutrophils.
abstract: We have reported that human autoantibodies reacting with the polymorphonuclear neutrophil (PMN)-anchored FcgammaRIIIb (CD16) protect these cells from spontaneous apoptosis. In this study, we used anti-CD16 F(ab')(2) to delineate the mechanism(s) whereby the PMN life span is extended. As documented using four methods, CD16 cross-linking impeded spontaneous apoptosis, whereas anti-CD18 F(ab')(2) exerted no effect. Incubation of PMNs with anti-CD16 prevented the up-regulation of beta(2) integrins, particularly CD11b, which is the alpha-chain of complement receptor type 3, but also CD18, which is its beta-chain, as well as CD11a and CD11c. Anti-CD16-conditioned supernatant of PMNs diminished the percentage of annexin V-binding fresh PMNs after another 18 h in culture, whereas the negative control anti-CD18 had no effect. The expression of mRNA for G-CSF and GM-CSF was induced by anti-CD16, followed by the release of G-CSF and GM-CSF in a dose-dependent manner. Anti-G-CSF and anti-GM-CSF mAbs abrogated the antiapoptotic effect of the related growth factors. The delay in apoptosis was accompanied by a down-regulated expression of Bax, and a partial reduction of caspase-3 activity. These data suggest an autocrine involvement of anti-CD16-induced survival factors in the rescue of PMNs from spontaneous apoptosis. Thus, apoptosis of aged PMNs can be modulated by signaling through FcgammaRIIIb, which may occur in patients with PMN-binding anti-FcgammaRIIIb autoantibodies.
authors.affiliation: Laboratory of Immunology, Institut de Synergie des Sciences et de la Santé, Brest University Medical School, 5 av. Foch, F 29 609 Brest Cedex, France.
authors.forename: V
authors.initials: V
authors.lastname: Durand
authors.forename: Y
authors.initials: Y
authors.lastname: Renaudineau
authors.forename: J O
authors.initials: JO
authors.lastname: Pers
authors.forename: P
authors.initials: P
authors.lastname: Youinou
authors.forename: C
authors.initials: C
authors.lastname: Jamin
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D017209:Apoptosis; D001685:Biological Factors / Q000096:biosynthesis; D018821:CD18 Antigens / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D058851:GPI-Linked Proteins; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000096:biosynthesis; D017452:Receptors, IgG / Q000276:immunology / Q000502:physiology*; D015533:Transcriptional Activation; D051028:bcl-2-Associated X Protein
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C494826:BAX protein, human; D001685:Biological Factors; D018821:CD18 Antigens; D017077:Culture Media, Conditioned; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017452:Receptors, IgG; D051028:bcl-2-Associated X Protein; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases