MIP-3 (cid:1) neutralizing monoclonal antibody protects against TNBS-induced colonic injury and inflammation in mice

MIP-3 (cid:1) neutralizing monoclonal antibody protects against TNBS-induced colonic injury and inflammation in mice. Am Physiol Gastrointest Liver Physiol G1263–G1271, 2007. characteristic feature of human inflammatory bowel disease, particularly Crohn’s disease, is the presence of activated CD4 (cid:2) T cells. Recently, we have shown that colonic epithelial cell production of macrophage inflammatory protein (MIP)-3 (cid:1) , a CD4 T cell-directed chemokine, is elevated in inflammatory bowel disease. However, the functional relevance of MIP-3 (cid:1) production during intestinal inflammation is poorly understood. The aim of this study was to determine whether MIP-3 (cid:1) production is increased during murine 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis and to examine the effect of anti-MIP-3 (cid:1) neutralizing monoclonal antibody administration in this model. We found that the administration of TNBS significantly increased colonic MIP-3 (cid:1) protein levels in Balb/c mice. Consistent with this, a marked increase in the number of CCR6-bearing lamina propria CD4 (cid:2) and CD8 (cid:2) T cells was also observed in TNBS-treated animals. Treatment of mice with an anti-MIP-3 (cid:1) 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-3 (cid:1) neutralizing monoclonal antibody treatment. Taken together, our findings indicate that blockade of MIP-3 (cid:1) bioactivity can significantly reduce TNBS-mediated colonic injury and T cell recruitment, suggesting a role for this chemokine in the pathophysiology of intestinal inflammation.

[1]  S. Brand,et al.  Cell differentiation dependent expressed CCR6 mediates ERK‐1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells , 2006, Journal of cellular biochemistry.

[2]  S. Jalkanen,et al.  Lymphocyte homing to the gut: attraction, adhesion, and commitment , 2005, Immunological reviews.

[3]  P. Allavena,et al.  Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells , 2005, Nature Immunology.

[4]  N. Hosoe,et al.  Increased lymphocyte trafficking to colonic microvessels is dependent on MAdCAM‐1 and C‐C chemokine mLARC/CCL20 in DSS‐induced mice colitis , 2005, Clinical and experimental immunology.

[5]  M. Kagnoff,et al.  Chemokine receptor CCR6 transduces signals that activate p130Cas and alter cAMP-stimulated ion transport in human intestinal epithelial cells. , 2005, American journal of physiology. Cell physiology.

[6]  R. Newberry,et al.  Inhibition of indoleamine 2,3-dioxygenase augments trinitrobenzene sulfonic acid colitis in mice. , 2003, Gastroenterology.

[7]  J. Flores,et al.  CCR6 has a non‐redundant role in the development of inflammatory bowel disease , 2003, European journal of immunology.

[8]  J. Van Damme,et al.  The CC chemokine CCL20 and its receptor CCR6. , 2003, Cytokine & growth factor reviews.

[9]  I. Williams,et al.  CCR6 expression distinguishes mouse myeloid and lymphoid dendritic cell subsets: demonstration using a CCR6 EGFP knock‐in mouse , 2002, European journal of immunology.

[10]  L. Lefrançois,et al.  Isolation of mouse small intestinal intraepithelial lymphocytes, Peyer's patch, and lamina propria cells. , 2001, Current protocols in immunology.

[11]  M. Leach,et al.  Characterization of chemokines and chemokine receptors in two murine models of inflammatory bowel disease: IL‐10– / – mice and Rag‐2– / – mice reconstituted with CD4+CD45RBhigh T cells , 2001, European journal of immunology.

[12]  P. Ricciardi-Castagnoli,et al.  Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria , 2001, Nature Immunology.

[13]  M. Kagnoff,et al.  Regulated MIP-3alpha/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity. , 2001, American journal of physiology. Gastrointestinal and liver physiology.

[14]  C. Martínez-A,et al.  CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses. , 2001, The Journal of clinical investigation.

[15]  S. Caughman,et al.  Cutting Edge: C-C Chemokine Receptor 6 Is Essential for Arrest of a Subset of Memory T Cells on Activated Dermal Microvascular Endothelial Cells Under Physiologic Flow Conditions In Vitro , 2000, The Journal of Immunology.

[16]  W. Gong,et al.  Expression of CCR6 and CD83 by cytokine-activated human neutrophils. , 2000, Blood.

[17]  C. Kelly,et al.  Interleukin 16 is up-regulated in Crohn's disease and participates in TNBS colitis in mice. , 2000, Gastroenterology.

[18]  C. Caux,et al.  Macrophage Inflammatory Protein 3α Is Expressed at Inflamed Epithelial Surfaces and Is the Most Potent Chemokine Known in Attracting Langerhans Cell Precursors , 2000, The Journal of experimental medicine.

[19]  J. Mcghee,et al.  Mice deficient in Th1- and Th2-type cytokines develop distinct forms of hapten-induced colitis. , 2000, Gastroenterology.

[20]  H. Greenberg,et al.  CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. , 2000, Immunity.

[21]  Y. Tanaka,et al.  Selective expression of liver and activation‐regulated chemokine (LARC) in intestinal epithelium in mice and humans , 1999, European journal of immunology.

[22]  C. Caux,et al.  Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites , 1998, The Journal of experimental medicine.

[23]  E. Butcher,et al.  Chemokines and the arrest of lymphocytes rolling under flow conditions. , 1998, Science.

[24]  A. Mantovani,et al.  Cloning and Characterization of a Specific Receptor for the Novel CC Chemokine MIP-3α from Lung Dendritic Cells , 1997, The Journal of experimental medicine.

[25]  J. Gutiérrez-Ramos,et al.  Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation , 1997, Nature.

[26]  Wei Wang,et al.  A new class of membrane-bound chemokine with a CX3C motif , 1997, Nature.

[27]  J. Mcghee,et al.  Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. , 1996, Journal of immunology.

[28]  A. Ben-Baruch,et al.  Signals and Receptors Involved in Recruitment of Inflammatory Cells (*) , 1995, The Journal of Biological Chemistry.

[29]  D. Largaespada,et al.  Lymphotactin: a cytokine that represents a new class of chemokine. , 1994, Science.

[30]  L. Mayer,et al.  Stimulation of lamina propria lymphocytes by intestinal epithelial cells: evidence for recognition of nonclassical restriction elements , 1994, The Journal of experimental medicine.

[31]  H. Tilg,et al.  Increased Expression of CCL20 in Human Inflammatory Bowel Disease , 2004, Journal of Clinical Immunology.

[32]  T. Matsui,et al.  Production of macrophage inflammatory protein 3alpha (MIP-3alpha) (CCL20) and MIP-3beta (CCL19) by human peripheral blood neutrophils in response to microbial pathogens. , 2003, Infection and immunity.

[33]  R. Colman,et al.  Experimental models of inflammatory bowel disease. , 2003, Archivum immunologiae et therapiae experimentalis.

[34]  L. Mayer,et al.  Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease. , 2002, Gut.

[35]  R. Blumberg,et al.  The immunology of mucosal models of inflammation. , 2002, Annual review of immunology.

[36]  P. Allavena,et al.  Neutrophils produce biologically active macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19. , 2001, European journal of immunology.

[37]  R. Rabin,et al.  CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha. , 1999, Journal of immunology.