PRIMING OF HUMAN POLYMORPHONUCLEAR NEUTROPHILIC LEUKOCYTES BY INSULIN-LIKE GROWTH-FACTOR-I - INCREASED PHAGOCYTIC CAPACITY, COMPLEMENT RECEPTOR EXPRESSION, DEGRANULATION, AND OXIDATIVE BURST

Insulin-like growth factor I (IGF-I) is a GH-dependent peptide regulat ing mammalian growth that seems to be of importance for the normal dev elopment and function of the immune system. Polymorphonuclear neutroph ilic leukocytes (PMNLs) are terminally differentiated phagocytes essen tial 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 augm ented the PMNL phagocytosis of both immunoglobulin G-opsonized Staphyl ococcus aureus and complement-opsonized Candida albicans. In addition, the growth factor increased PMNL complement receptor expression [comp lement receptors I (CD35) and 3 (CD11b)] and primed the cells to stron ger f-met-leu-phe-induced degranulation of both specific and azurophil ic granules [markers: CD11b, CD35 and CD67 (specific granules); CD63 ( azurophilic granules)]. In contrast, IGF-I did not alter the PMNL surf ace expression of Fc gamma RI (CD64), Fc gamma RII: (CDw32), or Fc gam ma RIII (CD16). PMNLs exposed to IGF-I increased their f-met-leu-phe a nd phorbol myristate acetate-induced oxidative burst, as evaluated by hydrogen peroxide production, whereas IGF-I did not influence PMNL act in polymerization. The priming of PMNLs by TGF-I was dependent on time and concentration, and saturating amounts of a monoclonal antibody to the IGF-I receptor blacked the priming of PMNLs by this peptide. Thes e experiments demonstrate that IGF-I can selectively stimulate mature PMNL functions, providing further evidence for the interaction between the immune and the endocrine systems.