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Abstract
A single encounter with a dialysis patient led to the study of complement and neutrophil aggregation, which in turn spawned our work and the remarkable development of the field of vascular biology. As our understanding of these cellular interactions and the signaling pathways involved in these processes has expanded, so has our appreciation for the broad impact of this work on an array of human diseases.
Authors
Gregory M. Vercellotti, Charles F. Moldow, Harry S. Jacob
Figure 1
Complement-activated neutrophil-mediated oxidant endothelial cell injury.
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Dialysis membranes activate complement to generate C5a. C5a binds to receptors (C5R) on endothelial cells and neutrophils (PMN), inducing P-selectin and activating the adhesion integrin CD11b/CD18. Neutrophil rolling on the selectin is followed by tight adhesion with proximate release of reactive oxygen species including O2–, H2O2, and HOCl, which mediate endothelial injury (measured by 51Cr release in vitro), endothelial gap formation with leak of plasma, and endothelial and NF-κB activation.
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)