The effect of citrate and other compounds on PMN incubated in vitro: further studies on the site and mechanism of action of citrate.

Polymorphonuclear leukocytes (PMN) are important in corneal disease because of their role as effector cells in inflammation and ulceration. The favorable effect of citrate on corneal ulceration appears to result from inhibition of the PMN. Citrate does not enter the cells but chelates Ca2+ in the extracellular fluid and may promote a loss of some intracellular Ca2+. Isocitrate is the only tricarboxylic acid cycle intermediate that inhibits PMN, also by Ca2+ chelation. When isobutylcyanoacrylate is polymerized, a substance, probably formaldehyde, inhibitory to PMN, continuously leeches from the plastic. Although acetylcysteine has been reported to inhibit collagenase in vitro it has a direct effect of enhancing the respiratory burst and possibly degranulation of PMN stimulated by opsonized zymosan. Dexamethasone had no effect on PMN stimulation while prednisolone was partially inhibitory at high concentrations. Indomethacin exerts an inhibitory effect on all parameters of PMN stimulation. These studies clarify the site and mechanism of citrate action as well as show the importance of knowing the effect of drugs on the PMN.