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Regulation of Eosinophil Adhesion by Lysophosphatidylcholine via a Non–Store-Operated Ca²⁺ Channel

Section of Pulmonary and Critical Care Medicine, Department of Medicine; and Department of Neurobiology, Pharmacology and Physiology, Pediatrics, Anesthesia and Critical Care, and Committees on Clinical Pharmacology, Cell Physiology and Molecular Medicine, Division of the Biological Sciences, The University of Chicago, Chicago, Illinois

Correspondence and requests for reprints should be addressed to Dr. Xiangdong Zhu, Section of Pulmonary and Critical Care Medicine, Department of Medicine, MC6076, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637. E-mail: xzhu{at}medicine.bsd.uchicago.edu

We examined the mechanism by which lysophosphatidylcholine (LPC) regulates ₂-integrin–mediated adhesion of eosiniophils. Eosinophils were isolated from blood of mildly atopic volunteers by negative immunomagnetic selection. ₂-integrin–dependent adhesion of eosinophils to plated bovine serum albumin (BSA) was measured by residual eosinophil peroxidase activity. LPC caused maximal adhesion of eosinophils to plated BSA at 4 µM. Lysophosphatidylinositol, which has a similar molecular shape, mimicked the effect of LPC on eosinophil adhesion, while neither lysophosphatidylserine nor lysophosphatidylethanolamine had any effect. Phosphatidylethanolamine, a lipid that has a molecular orientation that is the inverse of LPC, blocked eosinophil adhesion caused by LPC. Unlike platelet-activating factor, a G-protein–coupled receptor agonist, LPC did not cause Ca²⁺-store depletion, but caused increased Ca²⁺ influx upon addition of Ca²⁺ to extracellular medium. This influx was not inhibited by U73122, a phospholipase C inhibitor, demonstrating independence from the G protein–activated phospholipase C pathway. Ca²⁺ influx was inhibited by either preincubation of phosphotidylethanolamine or La³⁺, a broad spectrum blocker of cation channels. LPC induced up-regulation of the active conformation of CD11b, which was blocked by preincubation with phosphatidylethanolamine. These data suggest that LPC causes a non–store-operated Ca²⁺ influx into eosinophils, which subsequently activates CD11b/CD18 to promote eosinophil adhesion.

Key Words: lysophosphatidylcholine • eosinophils • adhesion • calcium

CLINICAL RELEVANCE This research focuses on the mechanisms by which lysophosphatidylcholine regulates eosinophil adhesion in vitro. This research will add to our knowledge of eosinophil infiltration in allergic inflammation, such as asthma.