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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 6, December, 2001 780-787

Hypoxia Mediates Increased Neutrophil and Macrophage Adhesiveness to Alveolar Epithelial Cells

Beatrice Beck-Schimmer, Ralph C. Schimmer, Caveh Madjdpour, John M. Bonvini, Thomas Pasch, and Peter A. Ward

Institutes of Anesthesiology and Physiology, University of Zurich, Zurich, Switzerland; Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; and Department of Orthopedic Surgery, University of Basel, Basel, Switzerland

Leukocyte infiltration is known to play an important role in hypoxia-induced tissue damage. There is a paucity of information on the role of hypoxia in the expression of adhesion molecules on respiratory epithelial cells. The current studies focus on the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), their expression pattern on alveolar epithelial cells, and their biologic function under hypoxic conditions. Rat alveolar epithelial cells (AEC) were exposed to hypoxia for several time periods. With 5% oxygen, mRNA for ICAM-1 and VCAM-1 rose by 100%, peaking between 0.5 and 1 h. ICAM-1 and VCAM-1 protein showed an increase between 2 and 4 h. Neutrophil adherence to hypoxia-exposed AEC was enhanced by 115%. This increase was reduced by 83% with anti-ICAM-1 antibody. Adherence of alveolar macrophages to AEC increased by 118% and could be blocked by 95% with anti-VCAM-1 antibody. The present study shows for the first time an early increase of ICAM-1 and VCAM-1 expression on rat AEC under hypoxic conditions. These adhesion molecules are involved in increased adhesiveness of neutrophils and macrophages. Such responses might play an important role in the adhesion of leukocytes and macrophages to lung epithelial cells during hypoxic conditions.

Abbreviations: actinomycin D, ACTD; alveolar epithelial cells, AEC; cycloheximide, CHX; Dulbecco's modified Eagle's medium, DMEM; enzyme-linked immunosorbent assay, ELISA; fetal bovine serum, FBS; reduced form of guanosine adenine dinucleotide phosphate, GAPDH; intercellular adhesion molecule-1, ICAM-1; lactate dehydrogenase, LDH; lipopolysaccharide, LPS; o-phenylenediamine dihydrochloride, OPD; phosphate-buffered saline, PBS; paraformaldehyde, PFA; polymorphonuclear cells, PMN; reverse transcription-polymerase chain reaction, RT-PCR; sodium dodecyl sulfate, SDS; standard saline citrate, SSC; tumor necrosis factor-alpha , TNF-alpha ; vascular cell adhesion molecule-1, VCAM-1.




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