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(Circulation Research. 2000;86:1237.)
© 2000 American Heart Association, Inc.

Cellular Biology

Postanoxic T Lymphocyte–Endothelial Cell Interactions Induce Tumor Necrosis Factor- Production and Neutrophil Adhesion

Role of Very Late Antigen-4/Vascular Cell Adhesion Molecule-1

Satoshi Kokura, Robert E. Wolf, Toshikazu Yoshikawa, D. Neil Granger, Tak Yee Aw

From the Department of Molecular and Cellular Physiology (S.K., D.N.G., T.Y.A.) and Center of Excellence in Arthritis and Rheumatism (R.E.W.), Louisiana State University Health Sciences Center, Shreveport, La, and First Department of Internal Medicine (T.Y.), Kyoto Prefectural University of Medicine, Kyoto, Japan.

Correspondence to Tak Yee Aw, PhD, Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932. E-mail taw{at}lsumc.edu

Abstract—The objective of this study was to define the influence of postanoxic T-lymphocyte–endothelial cell interactions on anoxia-reoxygenation (A/R)–induced neutrophil–endothelial cell adhesion and cell adhesion molecule (CAM) expression on human umbilical vein endothelial cells (HUVECs). HUVEC monolayers were exposed to 60 minutes of anoxia, followed by 24 hours of reoxygenation, wherein freshly isolated human T lymphocytes were added at 6 hours during reoxygenation. After an additional 18 hours of incubation (ie, total of 24 hours of reoxygenation), the T-cell/endothelial cell (TC/EC) coculture media were collected and added to naive HUVEC monolayers incubated with neutrophils. Although the A/R-conditioned media per se had no effect on neutrophil adhesion, the media from TC/EC cocultures significantly increased the adhesion response. This enhanced adhesive interaction was associated with significant increases in tumor necrosis factor- (TNF-) and interleukin-8 (IL-8) levels in the TC/EC coculture media and was accompanied by a pronounced increase in endothelial E-selectin expression. Treatment of the TC/EC coculture media with anti–TNF- or anti-IL-8 antibodies reduced the media-induced neutrophil adhesion response. The enhanced neutrophil adhesion and the elevated medium levels of TNF-, but not IL-8, were markedly reduced by inserts that prevented direct TC/EC contact and by monoclonal antibodies directed against vascular cell adhesion molecule-1 (VCAM-1) or very late antigen-4 (VLA-4). Collectively, these findings show that VLA-4–/VCAM-1–mediated interactions between T lymphocytes and postanoxic endothelial cells stimulates TNF- production, which in turn elicits endothelial cell adhesion molecule expression and a corresponding increase in neutrophil adhesion.

Key Words: anoxia/reoxygenation • E-selectin • neutrophil–endothelial cell adhesion • T lymphocytes • tumor necrosis-

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