Topical citrate inhibits the adherence of neutrophils to postcapillary venules

The high incidence of corneal ulceration in the alkali-injured rabbit eye can be reduced by topical citrate drops. Citrate interferes with polymorphonuclear leukocyte (PMN) accumulation in the corneal stroma after alkali injury. It inhibits the adherence, locomotion, respiratory burst, phagocytosis, and degranulation of human PMNs in vitro. The objective of this research was to determine if PMN adherence to the vascular endothelium could be inhibited by superfused citrate in vivo. PMN adherence to the endothelium of postcapillary venules in the hamster cheek pouch was greatly enhanced and maintained by addition of leukotriene B4 (LTB4) to the superfusate. Superfusion of the pouch with 24 mM citrate for 5 min, before addition of LTB4, inhibited PMN adherence to the endothelium. The free calcium level in the superfusate was reduced from approximately 650 to 33 microM in the presence of 24 mM citrate. When LTB4-augmented PMN adherence was allowed to occur, followed by citrate treatment (24 mM), it was reversed. Simultaneous addition of CaCl2 and MgCl2 to the superfusate raised the free Ca2+ level to 786 microM and reversed the citrate-induced inhibition of LTB4-augmented adherence. From this and other research, we conclude that citrate probably inhibits adherence of PMNs to pericorneal and conjunctival vessels in the eye, preventing their accumulation in the corneal stroma.