Effects of insulin-like growth factor-I and its analogues on bovine hydrogen peroxide release by neutrophils and blastogenesis by mononuclear cells.

Abstract

The biological potencies of recombinant human insulin-like growth factor-I (IGF-I) and two of its analogues were examined for hydrogen peroxide release by neutrophils and blastogenesis by mononuclear cells. The binding affinities of these peptides for bovine serum IGF-binding proteins (IGFBPs) and IGF-I receptors on bovine neutrophils and mononuclear cells were also investigated. Relative to control treatment containing no IGF-I, preincubation of neutrophils with 12.5 micrograms/l of IGF-I, des(1-3)IGF-I (an analogue of human IGF-I lacking the N-terminal tripeptide Gly-Pro-Glu) and long R3 IGF-I (an analogue of human IGF-I with arginine replacing glutamate at position 3 of human IGF-I and the N-terminal extension Met-Phe-Pro-Ala-Met-Pro-Leu-Ser-Ser-Leu-Phe-Val-Asn) increased the release of H2O2 by 65%, 64% and 32% respectively. However, the difference in stimulating the release of H2O2 between long R3 IGF-I and other two (IGF-I and des(1-3)IGF-I) was reduced at a dosage of 100 micrograms/l. In the absence or presence of 2.5% fetal calf serum (FCS), 100 micrograms/l of IGF-I, des(1-3)IGF-I but not long R3 IGF-I significantly stimulated thymidine incorporation into mononuclear cells. In addition, des(1-3)IGF-I was more potent than IGF-I in stimulating thymidine incorporation into mononuclear cells in the presence of 2.5% FCS.(ABSTRACT TRUNCATED AT 250 WORDS)