Priming of human polymorphonuclear neutrophilic leukocytes by insulin-like growth factor I: increased phagocytic capacity, complement receptor expression, degranulation, and oxidative burst.

Abstract

Insulin-like growth factor I (IGF-I) is a GH-dependent peptide regulating mammalian growth that seems to be of importance for the normal development and function of the immune system. Polymorphonuclear neutrophilic leukocytes (PMNLs) are terminally differentiated phagocytes essential for host defense, and in the present study, recombinant human IGF-I was shown to be a powerful primer of mature human PMNLs. IGF-I augmented the PMNL phagocytosis of both immunoglobulin G-opsonized Staphylococcus aureus and complement-opsonized Candida albicans. In addition, the growth factor increased PMNL complement receptor expression [complement receptors 1 (CD35) and 3 (CD11b)] and primed the cells to stronger f-met-leu-phe-induced degranulation of both specific and azurophilic granules [markers: CD11b, CD35 and CD67 (specific granules); CD63 (azurophilic granules)]. In contrast, IGF-I did not alter the PMNL surface expression of Fc gamma RI (CD64), Fc gamma RII (CDw32), or Fc gamma RIII (CD16). PMNLs exposed to IGF-I increased their f-met-leu-phe and phorbol myristate acetate-induced oxidative burst, as evaluated by hydrogen peroxide production, whereas IGF-I did not influence PMNL actin polymerization. The priming of PMNLs by IGF-I was dependent on time and concentration, and saturating amounts of a monoclonal antibody to the IGF-I receptor blocked the priming of PMNLs by this peptide. These experiments demonstrate that IGF-I can selectively stimulate mature PMNL functions, providing further evidence for the interaction between the immune and the endocrine systems.