Endothelial activation by hydrogen peroxide. Selective increases of intercellular adhesion molecule-1 and major histocompatibility complex class I
Bradley, J.R.; Johnson, D.R.; Pober, J.S.
American Journal of Pathology 142(5): 1598-1609
ISSN/ISBN: 0002-9440 PMID: 8098585 Accession: 009836279
Products of activated leukocytes may alter vascular endothelial cell (EC) function. For example, ECs respond to leukocyte-derived cytokines, such as tumor necrosis factor (TNF) or interleukin- 1, by reversibly altering levels of expression of specific gene products that promote inflammation. In contrast, hydrogen peroxide, a product of TNF-activated neutrophils, can produce irreversible EC injury and death. In this study, we have investigated the effects of subinjurious concentrations of hydrogen peroxide on EC inflammatory functions. Treatment with 50 to 100 mu-mol/L hydrogen peroxide selectively increases surface expression of intercellular adhesion molecule-1 and major histocompatibility complex class I, but not endothelial leukocyte adhesion molecule-1 (also known as E-selectin), vascular cell adhesion molecule-1 or gp96, a constitutively expressed EC surface protein. Increased major histocompatibility complex class I and intercellular adhesion molecule-1 surface expression is associated with specifically increased messenger P-NA levels, suggesting selective endothelial gene activation. Hydrogen peroxide does not activate the transcription factor Nuclear Factor kappa-B, an important mediator of TNF-induced gene expression. Cotreatment with hydrogen peroxide inhibits TNF-induced gene expression at 4 hours, an effect which can be attributed to reversible inhibition of TNF binding to EC surface receptors. Hydrogen peroxide also antagonizes the actions of interleukin-1. At 24 hours, TNF and hydrogen peroxide produce, at most, additive increases in intercellular adhesion molecule-1 and major histocompatibility complex class I. These results suggest that subinjurious concentrations of hydrogen peroxide can activate endothelium and that the effects of hydrogen peroxide on ECs differ from those of inflammatory cytokines.