Accession Number:

ADA618497

Title:

Platelet-Associated CD40/CD154 Mediates Remote Tissue Damage After Mesenteric Ischemia/Reperfusion Injury

Descriptive Note:

Journal article

Corporate Author:

ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX

Report Date:

2012-02-27

Pagination or Media Count:

8.0

Abstract:

Several innate and adaptive immune cells types participate in ischemiareperfusion induced tissue injury. Amongst them, platelets have received little attention as contributors in the process of tissue damage after ischemia reperfusion IR injury. It is currently unknown whether platelets participate through the immunologically important molecules including, CD40 and when activated, CD154 CD40L, in the pathogenesis of IR injury. We hypothesized that constitutive expression of CD40 and activation-induced expression of CD154 on platelets mediate local mesenteric and remote lung tissue damage after IR injury. Wild type WT C57BL6J, CD40 and CD154 deficient mice underwent mesenteric ischemia for 30 minutes followed by reperfusion for 3 hours. WT mice subjected to mesenteric IR injury displayed both local intestinal and remote lung damage. In contrast, there was significantly less intestinal damage and no remote lung injury in CD40 and CD154 deficient mice when compared to WT mice. Platelet-depleted WT mice transfused with platelets from CD40 or CD154 deficient mice failed to reconstitute remote lung damage. In contrast, when CD40 or CD154 deficient mice were transfused with WT platelets, lung tissue damage was reestablished. Together, these findings suggest that multiple mechanisms are involved in local and remote tissue injury and also identify platelet-expressed CD40 andor CD154 as mediators of remote tissue damage.

Subject Categories:

  • Biochemistry
  • Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE