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Lung Microvascular and Arterial Endothelial Cells Differ in Their Responses to Intercellular Adhesion Molecule-1 Ligation

Division of Integrative Biology, Department of Pediatrics, Rainbow Babies and Children's Hospital and Case Western Reserve University, Cleveland, Ohio; and Department of Pharmacology, University of South Alabama, Mobile, Alabama

Correspondence and requests for reprints should be addressed to Claire M. Doerschuk, M.D., Rainbow Babies and Children's Hospital and Case Western Reserve University, Room 787, 11100 Euclid Avenue, Cleveland, OH 44106. E-mail: cmd22{at}po.cwru.edu

Neutrophil adherence to tumor necrosis factor- (TNF-)–treated human pulmonary microvascular endothelial cells (PMECs) induces cytoskeletal changes in endothelial cells that require intercellular adhesion molecule-1 (ICAM-1)–dependent signaling events. This study determined whether similar changes occurred in rat PMECs and whether rat pulmonary arterial endothelial cells (PAECs) responded differently. Neutrophil adherence induced an increase in the formation of F-actin and in the apparent stiffness of TNF-–treated rat PMECs. These responses, however, were absent in PAECs. To determine the mechanisms underlying these differences, ICAM-1–mediated signaling events were compared. Upregulation of ICAM-1 by TNF- and redistribution of ICAM-1 induced by cross-linking antibodies were similar in both cell types. However, neutrophil adherence induced production of reactive oxygen species only in PMECs and not in PAECs. Moreover, phosphorylation of p38 mitogen-activated protein kinase induced by ICAM-1 cross-linking occurred only in PMECs and not in PAECs. This increase in p38 phosphorylation in PMECs was inhibited by allopurinol, a xanthine oxidase inhibitor. These data demonstrated that whereas TNF- upregulated ICAM-1 and ICAM-1 cross-linking induced a similar redistribution of ICAM-1 on the endothelial cell surface, ICAM-1 ligation initiated p38 activation and cytoskeletal rearrangements only in PMECs and not in PAECs. Thus, neutrophil adhesion through ICAM-1 induced signaling events leading to cytoskeletal changes only in PMECs, the site of neutrophil emigration and edema formation, and not in PAECs.

Key Words: intercellular adhesion molecule-1 • signaling • lung • endothelial cell

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