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- Title
T-Lymphocytes Modulate the Microvascular and Inflammatory Responses to Intestinal Ischemia-Reperfusion.
- Authors
Shigematsu, Takeharu; Wolf, Robert E; Granger, D Neil
- Abstract
Objective: The overall objective of this study was to define the contribution of T-lymphocytes to the microvascular and inflammatory responses of the intestine to ischemia/reperfusion (I/R). Methods: The superior mesenteric artery of wild-type (WT) and SCID mice was occluded for 45 minutes, followed by 30 minutes or 6 hours of reperfusion. Intravital fluorescence microscopy was used to monitor the extravasation of FITC-labeled albumin or the adhesion of carboxy-fluorescein diacetate succin-imidyl ester (CFSE)-labeled T-lymphocytes in mucosal venules of the postisch-emic intestine. Tissue myeloperoxidase (MPO) was used to monitor neutrophil accumulation in the intestine of WT and SCID mice. Results: Although the number of adherent T-cells was not increased above baseline at 1 hour after reperfusion, significant T-cell adhesion (both CD4[SUP+] and CD8[SUP+]) was noted at 6 hours of reperfusion. The latter response was prevented by pretreatment with a blocking antibody directed against MAdCAM-1, but not ICAM-1 or VCAM-1. A significant increase in MAdCAM-1 expression was noted in both lymphoid (Peyer's patch) and nonlymphoid regions of the postischemic small bowel. The early (30 minutes after reperfusion) albumin extravasation elicited by gut I/R in WT mice was reduced in SCID mice. Reconstitution of SCID mice with T-lymphocytes restored the albumin leakage response to WT levels. The increased intestinal MPO caused by I/R (6 hours of reperfusion) in WT mice was attenuated in SCID mice; with reconstitution of SCID mice with T-cells the MPO response was restored. Conclusions: These findings indicate that intestinal I/R is associated with the recruitment of CD4+ and CD8+ T-cells, which is mediated by endothelial MAdCAM-1. T-cells seem to modulate the recruitment of neutrophils that occurs hours after reperfusion as well as the increased albumin extravasation that occurs within minutes after reperfusion.
- Publication
Microcirculation, 2002, Vol 9, Issue 2, p99
- ISSN
1073-9688
- Publication type
Academic Journal
- DOI
10.1038/sj.mn.7800126