title: A novel role of growth hormone and insulin-like growth factor-I. Priming neutrophils for superoxide anion secretion.
abstract: Growth hormone (GH) and the GH-dependent growth promoting peptide, insulin-like growth factor-I (IGF-I), are both potent signals for priming human and porcine polymorphonuclear neutrophils (PMN) to secrete superoxide anion (O2-). PMA, opsonized-zymosan, or FMLP could all be used as triggering stimuli to demonstrate priming by GH or IGF-I. As positive controls, IFN-gamma and LPS also primed both human and porcine PMN for enhanced O2- release. However, only the LPS-mediated enhancement was inhibited by polymyxin B, which demonstrates that the priming induced by GH, IGF-I, or IFN-gamma was not caused by LPS contamination. Furthermore, a specific antibody to GH abrogated priming induced by this molecule. In contrast to IGF-I, the closely related molecule insulin was unable to prime PMN even at pharmacologic levels. Insulin, at pharmacologic levels, antagonized the priming mediated by IGF-I but had no effect on GH priming. A mAb directed against the human IGF-I receptor blocked the enhanced secretion of O2- by human PMN that was caused by IGF-I, but not GH, indicating that neutrophil priming induced by GH was not mediated by inducing extracellular release of IGF-I. However, priming PMN by both GH and IGF-I required de novo protein synthesis, because cycloheximide completely abrogated enhanced O2- secretion that was caused by these growth factors. These data show that a classic pituitary hormone (GH), as well as its widely recognized growth promoting peptide (IGF-I), are involved in regulating an important functional activity of both porcine and human PMN. Inasmuch as GH and IGF-I have recently been demonstrated to be synthesized by leukocytes, these data support the possibility that both of these proteins could act in a paracrine fashion as cytokines to prime PMN for an enhanced respiratory burst.
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana 61801.
authors.forename: Y K
authors.initials: YK
authors.lastname: Fu
authors.forename: S
authors.initials: S
authors.lastname: Arkins
authors.forename: B S
authors.initials: BS
authors.lastname: Wang
authors.forename: K W
authors.initials: KW
authors.lastname: Kelley
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D003513:Cycloheximide / Q000494:pharmacology; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D011994:Recombinant Proteins; D013481:Superoxides / Q000378:metabolism*; D013552:Swine
chemical_list: D000911:Antibodies, Monoclonal; D007328:Insulin; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D013481:Superoxides; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma; D013006:Growth Hormone; D003513:Cycloheximide; D011112:Polymyxin B