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Published online before print May 22, 2003

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(Journal of Leukocyte Biology. 2003;74:197-205.)
© 2003 by Society for Leukocyte Biology

Hypoxia reduces CD80 expression on monocytes but enhances their LPS-stimulated TNF- secretion

Nitza Lahat^*, Michal A. Rahat^*, Mouna Ballan^*,, Lea Weiss-Cerem, Miri Engelmayer^* and Haim Bitterman

^* Immunology Research Unit and
Ischemia-Shock Research Laboratory, Carmel Medical Center, Rappaport Family Institute for Research in the Medical Sciences, and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

Correspondence: Michal A. Rahat, D.Sc., Immunology Research Unit, Carmel Medical Center, 7 Michal St., Haifa, 34362, Israel. E-mail: rahat_miki{at}clalit.org.il

Monocytes/macrophages in ischemic tissues are involved in inflammation and suppression of adaptive immunity via secretion of proinflammatory cytokines and reduced ability to trigger T cells, respectively. We subjected human mononuclear cells and mouse macrophages to hypoxia and reoxygenation, the main constituents of ischemia and reperfusion, and added lipopolysaccharide (LPS) to simulate bacterial translocation, which frequently accompanies ischemia. We monitored the secretion of tumor necrosis factor (TNF-) and the surface expression of human leukocyte antigen-DR and the costimulatory molecules CD80 and CD86 on monocytes/macrophages. Hypoxia selectively reduced the surface expression of CD80 (P<0.01), and synergistically with LPS, it enhanced TNF- secretion (P<0.003). Reoxygenation reversed both phenomena. In the mouse macrophage cell line RAW 264.7, hypoxia reduced the surface expression of CD80 and increased its concentrations in the supernatants (P<0.01). Down-regulation of the mRNA coding for the membrane-anchored CD80 was observed, suggesting that hypoxia triggers alternative splicing to generate soluble CD80. Cumulatively, these results suggest that hypoxia simultaneously affects monocytes/macrophages to enhance inflammation and reduce their ability to initiate adaptive-immunity responses associated with ischemic injury.

Key Words: reoxygenation • CD86 • HLA-DR

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