T-lymphocytes modulate the microvascular and inflammatory responses to intestinal ischemia-reperfusion.
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 succinimidyl ester (CFSE)-labeled T-lymphocytes in mucosal venules of the postischemic 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(+) and CD8(+)) 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.
Shigematsu
Takeharu
T
Department of Molecular Cellular Physiology, Center of Excellence in Arthritis Rheumatology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Wolf
Robert E
RE
Granger
D Neil
DN
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007136:Immunoglobulins / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007422:Intestines / Q000098:blood supply*; D017538:Mesenteric Artery, Superior; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008833:Microcirculation / Q000503:physiopathology*; D009088:Mucoproteins / Q000502:physiology; D009504:Neutrophils / Q000201:enzymology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase