Oxidative priming of neutrophils by interferon-gamma.
Priming of neutrophil (PMN) oxidative responses is an integral component of host defense and inflammation and may contribute to cell-mediated tissue injury. The characteristics and mechanisms of interferon-gamma (IFN-gamma)-induced oxidative priming of PMNs were explored in vitro. Following pretreatment of human PMNs with recombinant IFN-gamma, superoxide anion release was selectively primed toward the receptor-initiated stimulants f-Met-Leu-Phe (fMLP) and C5a but not toward the transduction-mediated stimulants phorbol myristate acetate and A23187, a calcium ionophore. IFN-gamma also induced priming toward the stimulant NaF, a direct activator of guanine nucleotide regulatory proteins. Priming was not associated with changes in fMLP surface receptor expression or degranulation. Priming was dependent on de novo mRNA and protein synthesis. The immuno-regulatory lymphokine IFN-gamma primes PMN oxidative responses, apparently via production of proteins that are involved in the early postreceptor transductional pathways of oxidative metabolism.
Department of Surgery, Wayne State University School of Medicine, Allen Park Veterans Affairs Medical Center, Detroit, Michigan 48101.
S D
SD
Tennenberg
D E
DE
Fey
M J
MJ
Lieser
D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005966:Glucuronidase / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009247:NADH, NADPH Oxidoreductases / Q000097:blood; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D011113:Polymyxins / Q000494:pharmacology; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D011113:Polymyxins; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D003609:Dactinomycin; D007371:Interferon-gamma; D003513:Cycloheximide; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D005966:Glucuronidase