Trefoil peptide TFF2 treatment reduces VCAM-1 expression and leukocyte recruitment in experimental intestinal inflammation

2003 ◽  
Vol 75 (2) ◽  
pp. 214-223 ◽  
Author(s):  
Antonio Soriano-Izquierdo ◽  
Meritxell Gironella ◽  
Anna Massaguer ◽  
Felicity E. B. May ◽  
Antonio Salas ◽  
...  
2008 ◽  
Vol 1 (1) ◽  
pp. 57-61 ◽  
Author(s):  
Sean Kessler ◽  
Hyunjin Rho ◽  
Gail West ◽  
Claudio Fiocchi ◽  
Judith Drazba ◽  
...  

2003 ◽  
Vol 284 (5) ◽  
pp. G729-G733 ◽  
Author(s):  
Claudine S. Bonder ◽  
Paul Kubes

A hallmark feature of intestinal inflammation is the recruitment and extravasation of numerous cell types from the blood to the afflicted site. Much of what we know about the mechanisms of leukocyte recruitment to splanchnic organs comes from an extensive series of studies on neutrophils in the mesenteric microvasculature. In this themes article, we highlight the important findings from these experiments but also emphasize some of the limitations. In fact, there is a growing body of evidence that neutrophil recruitment may be quite different in the mesentery than in other splanchnic organs. For example, the molecular mechanisms underlying neutrophil recruitment into the liver are quite different than the mesentery and are dependent on the type of inflammatory disease. We also discuss the effect of modulating leukocyte recruitment to splanchnic organs in chronic inflammation and emphasize that the approaches that have been successful in acute inflammation may be less effective in such conditions as inflammatory bowel disease (IBD). One obvious reason for this observation is the growing body of evidence to suggest that the initiation and maintenance of IBD is, in part, due to dysregulated or inappropriately activated populations of infiltrating T lymphocyte subsets. Therefore, we also discuss some interesting new approaches to limiting lymphocyte recruitment into the inflamed intestine either by targeting T helper (Th)1 vs. Th2 lymphocytes or perhaps by allowing the recruitment of regulatory T cells. Inhibiting specific adhesion molecules or specific chemokine receptors may work in this regard.


2004 ◽  
Vol 287 (1) ◽  
pp. G115-G124 ◽  
Author(s):  
Emile M. Rijcken ◽  
Mike G. Laukoetter ◽  
Christoph Anthoni ◽  
Stephanie Meier ◽  
Rudolf Mennigen ◽  
...  

Recruitment of circulating leukocytes into the colonic tissue is a key feature of intestinal inflammation. P-selectin glycoprotein ligand-1 (PSGL-1) and very late antigen-4 (VLA-4) are expressed on leukocytes and play an important role in leukocyte-endothelial cell adhesive interactions. We examined the effects of immunoneutralization of PSGL-1 and VLA-4 on leukocyte recruitment in vivo in the development and treatment of experimental colitis. Chronic colitis was induced in balb/c mice by oral administration of dextran sodium sulfate (DSS). Monoclonal antibodies 2PH1 (anti-PSGL-1) and PS/2 (anti-VLA-4) or the combination of both were injected intravenously, and leukocyte adhesion was observed for 60 min in colonic submucosal venules by intravital microscopy (IVM) under isoflurane/N2O anesthesia. In addition, mice with established colitis were treated by daily intraperitoneal injections of 2PH1, PS/2, or the combination of both over 5 days. Disease activity index (DAI), histology, and myeloperoxidase (MPO) levels were compared with sham-treated DSS controls. We found that 2PH1 reduced the number of rolling leukocytes (148.7 ± 29.8 vs. 36.9 ± 8.7/0.01 mm2/30 s, P < 0.05), whereas leukocyte velocity was increased (24.0 ± 3.6 vs. 127.8 ± 11.7 μm/s, P < 0.05). PS/2 reduced leukocyte rolling to a lesser extent. Leukocyte firm adhesion was not influenced by 2PH1 but was strongly reduced by PS/2 (24.1 ± 2 vs. 4.4 ± 0.9/0.01 mm2/30 s, P < 0.05). Combined application did not cause additional effects on leukocyte adhesion. Treatment of chronic colitis with 2PH1 or PS/2 reduced DAI, mucosal injury, and MPO levels significantly. Combined treatment led to a significantly better reduction of DAI (0.4 ± 0.1 vs. 2.1 ± 0.2 points) and histology (9.7 ± 0.9 vs. 21.4 ± 4.6 points). In conclusion, PSGL-1 and VLA-4 play an important role for leukocyte recruitment during intestinal inflammation. Therapeutic strategies designed to disrupt interactions mediated by PSGL-1 and/or VLA-4 may prove beneficial in treatment of chronic colitis.


2010 ◽  
Vol 299 (1) ◽  
pp. G43-G53 ◽  
Author(s):  
P. L. Beck ◽  
E. Ihara ◽  
S. A. Hirota ◽  
J. A. MacDonald ◽  
D. Meng ◽  
...  

Intestinal mucosal integrity is dependent on epithelial function and a regulated immune response to injury. Fucosyltransferase VII (Fuc-TVII) is an essential enzyme required for the expression of the functional ligand for E- and P-selectin. Trefoil factor 3 (TFF3) is involved in both protecting the intestinal epithelium against injury as well as aiding in wound repair following injury. The aim of the present study was to assess the interplay between barrier function and leukocyte recruitment in intestinal inflammation. More specifically, we aimed to examine how targeted disruption of Fuc-TVII either in wild-type or TFF3−/− mice would alter their susceptibility to colonic injury. TFF3 and Fuc-TVII double-knockout mice (TFF3/Fuc-TVII−/− mice) were generated by mating TFF3−/− and Fuc-TVII−/− mice. Colitis was induced by administration of dextran sodium sulfate (DSS) (2.5% wt/vol) in the drinking water. Changes in baseline body weight, diarrhea, and fecal blood were assessed daily. Upon euthanasia, extents of colonic inflammation were assessed macroscopically, microscopically, and through quantification of myeloperoxidase (MPO) activity. Colonic lymphocyte subpopulations were assessed at 6 days after administration of DSS by flow cytometry and immunohistochemistry. No baseline intestinal inflammation was found in TFF3/Fuc-TVII−/−, TFF3−/−, Fuc-TVII−/−, or wild-type mice. Loss of Fuc-TVII resulted in a reduction in disease severity whereas TFF3−/− mice were markedly more susceptible to DSS-induced colitis. Remarkably, the loss of Fuc-TVII in TFF3−/− mice markedly decreased the severity of DSS-induced colitis as evidenced by reduced weight loss, diarrhea, decreased colonic MPO levels and improved survival. Furthermore, the loss of TFF3 resulted in increased severity of spontaneous colitis in IL-2/β-microglobulin-deficient mice. These studies highlight the importance of the interplay between factors involved in the innate immune response, mucosal barrier function, and genes involved in regulating leukocyte recruitment and other aspects of the immune response.


2001 ◽  
Vol 120 (5) ◽  
pp. A182-A182
Author(s):  
G GREGORY ◽  
W STENSON ◽  
R NEWBERRY

2001 ◽  
Vol 120 (5) ◽  
pp. A182-A183
Author(s):  
M HAUSMANN ◽  
S MESTERMANN ◽  
T SPOETTI ◽  
J SCHOELMERICH ◽  
T ANDUS ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A517-A517
Author(s):  
A MIZOGUCHI ◽  
E MIZOGUCHI ◽  
Y DEJONG ◽  
H TAKEDATSU ◽  
F PREFFER ◽  
...  

2020 ◽  
Vol 158 (3) ◽  
pp. S66
Author(s):  
Venu Lagishetty ◽  
Nerea Arias ◽  
Tien Dong ◽  
Meg Hauer ◽  
William Katzka ◽  
...  

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
L Marx ◽  
D Grundmann ◽  
D Schreiber ◽  
D Simon ◽  
A Braun ◽  
...  

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