Polymorphonuclear leukocytic inhibition by citrate, other metal chelators, and trifluoperazine. Evidence to support calcium binding protein involvement.
Corneal ulceration after severe alkali burns of the eye is thought to result principally from collagen breakdown as a consequence of local polymorphonuclear leukocyte (PMN) activities. The favorable effect of topical citrate on such burns suggested a direct effect on these inflammatory cells. These in vitro studies show that the stimulation of human PMN by opsonized zymosan can be inhibited by citrate, EDTA, and EGTA. These compounds interfere with opsonized zymosan attachment to PMN, preventing the respiratory burst, phagocytosis, and degranulation. Reversal of this inhibition by calcium and/or magnesium suggests that mechanism is calcium chelation. Trifluoperazine (TFP) inhibition of opsonized zymosan attachment and phagocytosis implicates the involvement of calmodulin. We propose that citrate, EDTA, and EGTA interfere with the receptor mediated attachment of opsonized zymosan to the PMN cell membrane, leaving the PMN in a resting, granulated state. Inhibition of the receptor system by calcium depletion may be the result of interference with calcium-calmodulin modulated microfilament and/or microtubule interfaces in the PMN plasma membrane. It is postulated that comparable events occur in the citrate treated alkali burned cornea. Citrate inhibition of PMN may be useful in other eye and systemic diseases.
D002056:Burns / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002951:Citrates / Q000378:metabolism / Q000494:pharmacology*; D019343:Citric Acid; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D010587:Phagocytosis; D014268:Trifluoperazine / Q000494:pharmacology; D015054:Zymosan / Q000378:metabolism
D002147:Calmodulin; D002951:Citrates; D014268:Trifluoperazine; D019343:Citric Acid; D004533:Egtazic Acid; D015054:Zymosan; D004492:Edetic Acid; D002118:Calcium