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Mast-cell-dependent secretion of CXC chemokines regulates ischemia-reperfusion-induced leukocyte recruitment in the colon.

Santén, Stefan LU ; Wang, Yusheng LU ; Menger, Michael; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2008) In International Journal of Colorectal Disease 23. p.527-534
Abstract
BACKGROUND AND AIMS: 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. MATERIALS AND 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... (More)
BACKGROUND AND AIMS: 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. MATERIALS AND 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. CONCLUSION: 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Colorectal Disease
volume
23
pages
527 - 534
publisher
Springer
external identifiers
  • pmid:18193431
  • wos:000254200900011
  • scopus:41149086245
ISSN
1432-1262
DOI
10.1007/s00384-007-0436-2
language
English
LU publication?
yes
id
04ea31ff-9cf8-4e0c-a284-80885bf59d17 (old id 1021404)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18193431?dopt=Abstract
date added to LUP
2008-02-13 15:11:10
date last changed
2017-07-09 04:31:56
@article{04ea31ff-9cf8-4e0c-a284-80885bf59d17,
  abstract     = {BACKGROUND AND AIMS: 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. MATERIALS AND 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. CONCLUSION: 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.},
  author       = {Santén, Stefan and Wang, Yusheng and Menger, Michael and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {1432-1262},
  language     = {eng},
  pages        = {527--534},
  publisher    = {Springer},
  series       = {International Journal of Colorectal Disease},
  title        = {Mast-cell-dependent secretion of CXC chemokines regulates ischemia-reperfusion-induced leukocyte recruitment in the colon.},
  url          = {http://dx.doi.org/10.1007/s00384-007-0436-2},
  volume       = {23},
  year         = {2008},
}