Igf-I Inhibits Spontaneous Apoptosis in Human Granulocytes

Endocrinology. 2002 Apr;143(4):1206-12. doi: 10.1210/endo.143.4.8725.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Annexin A5 / metabolism
  • Apoptosis / drug effects*
  • Cells, Cultured
  • DNA Fragmentation
  • Granulocytes / drug effects*
  • Granulocytes / metabolism
  • Granulocytes / ultrastructure
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Insulin-Like Growth Factor I / pharmacology*
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Radioligand Assay
  • Receptor, IGF Type 1 / biosynthesis
  • Recombinant Proteins / pharmacology
  • Stimulation, Chemical
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Annexin A5
  • Indicators and Reagents
  • Interleukin-6
  • Interleukin-8
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1