The effects of citrate on fMLP-induced polymorphonuclear leukocyte stimulation and locomotion.
Citrate reduces the incidence of corneal ulceration and perforation in alkali burned eyes and prevents polymorphonuclear leukocyte (PMN) accumulation in certain inflamed ocular tissues. Chelation of Ca2+ and Mg2+ by citrate appears to be the mechanism causing strong inhibition of in vitro PMN stimulation by opsonized zymosan. It is important to know if other activating agents of PMNs, with differing sensitivity to divalent cations, are inhibited by citrate. Citrate (12 mM) partially inhibits fMLP stimulation of the respiratory burst (50%) and degranulation (65%) of PMNs in a divalent cation free media, while having no effect or only a small effect in the presence of 1 mm Ca2+. Citrate also caused significant inhibition of fMLP (12 mM = 50%) induced locomotion of PMN when incubated in media containing 500 microM Ca2+ and 600 microM Mg2+ in a modified Boyden chamber. When used together, Ca2+ (6 mM) and Mg2+ (6 mM) reduced this inhibition to only 20%. Citrate apparently inhibits fMLP-induced stimulation in cation free media by chelating CA2+ effluxed from intracellular storage sites. In the chemotactic studies, citrate probably chelates extracellular Ca2+ and Mg2+. The divalent cation requirements of the activating agents and/or the PMN function may determine the degree of inhibition by citrate. It is therefore important to identify the mediators in alkali burned corneas as well as other inflammatory conditions.
D002118:Calcium / Q000494:pharmacology; D002464:Cell Migration Inhibition; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D004305:Dose-Response Relationship, Drug; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010101:Oxygen Consumption / Q000187:drug effects
D002951:Citrates; D019343:Citric Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005966:Glucuronidase; D008274:Magnesium; D002118:Calcium