Mast-cell-dependent secretion of CXC chemokines regulates ischemia-reperfusion-induced leukocyte recruitment in the colon.
OBJECTIVE
Recruitment of leukocytes in the tissue microvasculature is considered to be a rate-limiting step in ischemia-reperfusion (I/R)-induced inflammation. The objective of this study was to examine the role of mast cells in CXC-chemokine- and I/R-provoked leukocyte recruitment in the colon.


METHODS
Balb/c- and mast-cell-deficient mice were challenged with the CXC chemokines macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC) for 3 h. Leukocyte-endothelium interactions in the colonic microvascular bed were analyzed using an inverted intravital fluorescence microscopy technique. In separate experiments, mice were subjected to I/R by clamping of the superior mesenteric artery for 30 min followed by 120 min of reperfusion.


RESULTS
MIP-2 and KC induced a clear-cut increase in the number of rolling and adherent leukocytes in the colon. I/R increased the expression of MIP-2 and KC as well as leukocyte rolling and adhesion in the large bowel. Interestingly, leukocyte rolling and adhesion was reduced by more than 91% in mast-cell-deficient mice in response to CXC chemokine challenge. Moreover, I/R-induced leukocyte rolling and adhesion was decreased by more than 57% in mast-cell-deficient animals. Administration of MIP-2 increased the colonic expression of E-selectin mRNA in wild type but not in mast-cell-deficient mice.


CONCLUSIONS
Our data demonstrate that CXC chemokine-induced leukocyte rolling and adhesion is regulated by mast cells. Moreover, these findings also show that mast cells play a crucial role in supporting I/R-induced leukocyte rolling and adhesion in the colonic microvascular bed via secretion of CXC chemokines.
Santen
Stefan
S
Department of Surgery, Malmö University Hospital, Lund University, 20502 Malmö, Sweden.
Wang
Yusheng
Y
Menger
Michael D
MD
Jeppsson
Bengt
B
Thorlacius
Henrik
H
D000818:Animals; D002448:Cell Adhesion; D054426:Chemokine CXCL2 / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism*; D003106:Colon / Q000098:blood supply* / Q000276:immunology*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology*; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008833:Microcirculation / Q000276:immunology; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D019040:E-Selectin; D019007:P-Selectin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha