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MIP-3alpha neutralizing monoclonal antibody protects against TNBS-induced colonic injury and inflammation in mice

Katchar, Kianoosh ; Kelly, Ciarán P ; Keates, Sarah ; O'brien, Michael J ; Keates, Andrew C

American journal of physiology: Gastrointestinal and liver physiology, 2007-05, Vol.292 (5), p.G1263 [Periódico revisado por pares]

United States

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Título:
MIP-3alpha neutralizing monoclonal antibody protects against TNBS-induced colonic injury and inflammation in mice
Autor: Katchar, Kianoosh ; Kelly, Ciarán P ; Keates, Sarah ; O'brien, Michael J ; Keates, Andrew C
Assuntos: Animals ; Antibodies, Monoclonal - therapeutic use ; CD4 Lymphocyte Count ; CD8 Antigens - analysis ; Chemokine CCL20 ; Chemokines, CC - immunology ; Colitis - immunology ; Colitis - prevention & control ; Colonic Diseases - chemically induced ; Colonic Diseases - prevention & control ; Intestinal Mucosa - metabolism ; Macrophage Inflammatory Proteins - immunology ; Male ; Mice ; Mice, Inbred BALB C ; Trinitrobenzenesulfonic Acid ; Up-Regulation
É parte de: American journal of physiology: Gastrointestinal and liver physiology, 2007-05, Vol.292 (5), p.G1263
Descrição: A characteristic feature of human inflammatory bowel disease, particularly Crohn's disease, is the presence of activated CD4(+) T cells. Recently, we have shown that colonic epithelial cell production of macrophage inflammatory protein (MIP)-3alpha, a CD4 T cell-directed chemokine, is elevated in inflammatory bowel disease. However, the functional relevance of MIP-3alpha production during intestinal inflammation is poorly understood. The aim of this study was to determine whether MIP-3alpha production is increased during murine 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis and to examine the effect of anti-MIP-3alpha neutralizing monoclonal antibody administration in this model. We found that the administration of TNBS significantly increased colonic MIP-3alpha protein levels in Balb/c mice. Consistent with this, a marked increase in the number of CCR6-bearing lamina propria CD4(+) and CD8(+) T cells was also observed in TNBS-treated animals. Treatment of mice with an anti-MIP-3alpha neutralizing monoclonal antibody significantly reduced TNBS-mediated increases in colonic weight-to-length ratio, mucosal ulceration, histological damage, and myeloperoxidase activity. TNBS-mediated increases in the number of CCR6-bearing lamina propria T cells were also substantially reduced by anti-MIP-3alpha neutralizing monoclonal antibody treatment. Taken together, our findings indicate that blockade of MIP-3alpha bioactivity can significantly reduce TNBS-mediated colonic injury and T cell recruitment, suggesting a role for this chemokine in the pathophysiology of intestinal inflammation.
Editor: United States
Idioma: Inglês

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MIP-3alpha neutralizing monoclonal antibody protects against TNBS-induced colonic injury and inflammation in mice

Katchar, Kianoosh ; Kelly, Ciarán P ; Keates, Sarah ; O'brien, Michael J ; Keates, Andrew C

United States

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