Igf-I inhibits spontaneous apoptosis in human granulocytes.
Granulocytes are key cells in inflammatory processes that are recruited to sites of inflammation by chemoattractants such as IL-8 produced by neutrophils and monocytes. Programmed cell death (apoptosis) of granulocytes and subsequent recognition and phagocytosis by macrophages is a crucial mechanism for resolution of inflammation. Because IGF-I is a potent antiapoptotic factor, we addressed the effects of IGF-I on in vitro apoptosis of human peripheral blood granulocytes. We detected 1390 +/- 467 IGF-I receptors with a dissociation constant of 2.3 +/- 0.9 nM on purified granulocytes. Using microscopical analysis, annexin V binding assays to detect relocation of phosphatidylserine to the cell surface, and DNA fragmentation assays, we showed that IGF-I inhibits spontaneous apoptosis of granulocytes in serum-free culture by 32-45%. IGF-I did not modulate the secretion of IL-6, TNF alpha, and IL-8 by granulocytes, but IL-8 secretion by peripheral blood mononuclear cells was enhanced by 40%. These observations indicate that IGF-I may promote granulocyte functions by increasing granulocyte longevity.
Kooijman
Ron
R
Department of Pharmacology, Medical School, Vrije Universiteit Brussel, B-1090 Brussels, Belgium. rkooi@farc.vub.ac.be
Coppens
Astrid
A
Hooghe-Peters
Elisabeth
E
D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D053938:DNA Fragmentation; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017304:Annexin A5; D007202:Indicators and Reagents; D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1