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Aspirin-induced, neutrophil-mediated injury to vascular endothelium

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Abstract

Previous studies indicate that aspirin can promote neutrophil (PMN) adhesion to endothelial cells and neutrophil-mediated endothelial cell detachment. The objectives of the present study were to determine whether PMN adhesion is a pre-requisite for aspirin-induced, PMN-mediated endothelial cell detachment and whether neutrophil-derived oxidants and/or proteases are responsible for the cell detachment. Human PMNs were added to confluent monolayers of human umbilical vein endothelial cells (HUVEC) and coincubated with or without aspirin at a clinically relevant concentration (300μg/ml). Aspirin-activated PMNs induced endothelial cell detachment, but not cell lysis. Endothelial cell detachment was always preceded by retraction of endothelial cells within the monolayer. The aspirin-induced, neutrophilmediated cell detachment was prevented by a monoclonal antibody directed against CD11/CD18 adhesion integrins on PMNs. Elastase inhibitors, but not superoxide dismutase or catalase, prevented both endothelial cell retraction and detachment. If aspirin-activated neutrophils were allowed to migrate across the monolayers, endothelial cell retraction or detachment did not occur. These studies indicate that aspirin-induced, PMN-mediated endothelial cell retraction and detachment requires PMN adhesion to the target cells and is due to neutrophil-derived elastase. Endothelial cell retraction, induced by activated neutrophils, may represent an exaggeration of a normal physiologic event, i.e., neutrophil emigration.

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Author notes

  1. Peter R. Kvietys

    Present address: Victoria Hospital Research Institute, 375 South Street, Rm C206, N6A 4G5, London, Ontario, Canada

Authors and Affiliations

  1. Departments of Physiology and Medicine Center of Excellence for Arthritis and Rheumatology, Louisiana State University Medical Center, Shreveport, Louisiana

    Norimasa Yoshida, Gediminas Cepinskas, D. Neil Granger, Donald C. Anderson, Robert E. Wolf & Peter R. Kvietys

  2. Upjohn Laboratories, Kalamazoo, Michigan

    Norimasa Yoshida, Gediminas Cepinskas, D. Neil Granger, Donald C. Anderson, Robert E. Wolf & Peter R. Kvietys

Authors
  1. Norimasa Yoshida
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  2. Gediminas Cepinskas
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  3. D. Neil Granger
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  4. Donald C. Anderson
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  5. Robert E. Wolf
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Additional information

Supported by grants from the National Institutes of Health (DK 41399, DK 43785, HL 48855).

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Yoshida, N., Cepinskas, G., Granger, D.N. et al. Aspirin-induced, neutrophil-mediated injury to vascular endothelium. Inflammation 19, 297–312 (1995). https://doi.org/10.1007/BF01534389

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