Advertisement

Research Article Free access | 10.1172/JCI116122

Hypoxia-mediated induction of endothelial cell interleukin-1 alpha. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface.

R Shreeniwas, S Koga, M Karakurum, D Pinsky, E Kaiser, J Brett, B A Wolitzky, C Norton, J Plocinski, and W Benjamin

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Shreeniwas, R. in: PubMed | Google Scholar

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Koga, S. in: PubMed | Google Scholar

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Karakurum, M. in: PubMed | Google Scholar

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Pinsky, D. in: PubMed | Google Scholar

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Kaiser, E. in: PubMed | Google Scholar

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Brett, J. in: PubMed | Google Scholar

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Wolitzky, B. in: PubMed | Google Scholar

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Norton, C. in: PubMed | Google Scholar

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Plocinski, J. in: PubMed | Google Scholar

Department of Physiology, Columbia University, College of Physicians and Surgeons, New York 10032.

Find articles by Benjamin, W. in: PubMed | Google Scholar

Published December 1, 1992 - More info

Published in Volume 90, Issue 6 on December 1, 1992
J Clin Invest. 1992;90(6):2333–2339. https://doi.org/10.1172/JCI116122.
© 1992 The American Society for Clinical Investigation
Published December 1, 1992 - Version history
View PDF
Abstract

Tissue injury that accompanies hypoxemia/reoxygenation shares features with the host response in inflammation, suggesting that cytokines, such as IL-1, may act as mediators in this setting. Human endothelial cells (ECs) subjected to hypoxia (PO2 approximately 12-14 Torr) elaborated IL-1 activity into conditioned media in a time-dependent manner; this activity was completely neutralized by an antibody to IL-1 alpha. Production of IL-1 activity by hypoxic ECs was associated with an increase in the level of mRNA for IL-1 alpha, and was followed by induction of endothelial-leukocyte adhesion molecule-1 and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) during reoxygenation. During reoxygenation there was a three- to five-fold increased adherence of leukocytes, partly blocked by antibodies to endothelial-leukocyte adhesion molecule-1 and ICAM-1. Suppressing endothelial-derived IL-1, using either antibodies to IL-1 alpha, specific antisense oligonucleotides or the IL-1 receptor antagonist, decreased leukocyte adherence to reoxygenated ECs, emphasizing the integral role of IL-1 in the adherence phenomenon. Mice subjected to hypoxia (PO2 approximately 30-40 Torr) displayed increased plasma levels of IL-1 alpha, induction of IL-1 alpha mRNA in the lung, and enhanced expression of ICAM-1 in pulmonary tissue compared with normoxic controls. These data suggest that hypoxia is a stimulus which induces EC synthesis and release of IL-1 alpha, resulting in an autocrine enhancement in the expression of adhesion molecules.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (December 1, 1992): No description
Advertisement
Advertisement