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Release of Soluble E-Selectin from Activated Endothelial Cells upon Apoptosis

  • PULMONARY VASCULAR ENDOTHELIUM
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Abstract

Circulating soluble E-selectin is increased in diseases associated with endothelial apoptosis such as sepsis and acute respiratory distress syndrome. We investigated the mechanism by which endothelial cell (EC) apoptosis may promote soluble E-selectin release. We found that serum deprivation of EC caused apoptosis, yet it did not induce E-selectin EC surface expression. Tumor necrosis factor-α (TNFα) significantly increased EC E-selectin surface expression. Soluble E-selectin was noted, however, only in the medium of TNFα-activated, apoptotic EC. Preincubation of the EC with the caspase inhibitor z-VAD-fmk significantly attenuated soluble E-selectin levels in the culture medium of TNFα-activated, apoptotic EC, but it had no effect on E-selectin surface expression. These results indicate that TNFα activation, but not apoptosis, is necessary for E-selectin surface expression in EC. Furthermore, E-selectin release from EC requires caspase-3 activation. Thus, increased concentrations of circulating E-selectin in serum may serve as a marker for endothelial apoptosis in certain disease states.

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Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Providence VA Medical Center and supported with VA Merit Review and NIH HL64936 grants to S. Rounds and VA Merit Review and NIH HL67795 grants to E.O. Harrington. Some of these results were presented at the 2004 American Thoracic Society International Conference and were published in abstract form in American Journal of Respiratory and Critical Care Medicine 169:A23, 2004.

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Authors and Affiliations

  1. Vascular Research Laboratory, Providence Veterans Affairs Medical Center, Department of Medicine, Brown Medical School, Providence, Rhode Island

    Elizabeth O. Harrington, Julie Newton & Sharon Rounds

  2. Memorial Hospital, Pawtucket, Rhode Island

    Tihomir Stefanec

  3. Brown Medical School, Providence VA Medical Center, 830 Chalkstone Avenue, Providence, RI, 02908, USA

    Elizabeth O. Harrington

Authors
  1. Elizabeth O. Harrington
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  2. Tihomir Stefanec
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  3. Julie Newton
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  4. Sharon Rounds
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Correspondence to Elizabeth O. Harrington.

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E. O. Harrington and J. Newton contributed equally to this work.

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Harrington, E.O., Stefanec, T., Newton, J. et al. Release of Soluble E-Selectin from Activated Endothelial Cells upon Apoptosis. Lung 184, 259–266 (2006). https://doi.org/10.1007/s00408-005-2589-5

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  • DOI: https://doi.org/10.1007/s00408-005-2589-5

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