| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Gastrointestinal Unit, Department of Medicine, Center for the Study of Inflammatory Bowel Disease, and
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC;
§
Department of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712; and
¶
Division of Gastroenterology, Albany Medical College, Albany, NY 12208
The chemokine receptors CCR2 and CCR5 and their respective ligands
regulate leukocyte chemotaxis and activation. To determine the role of
these chemokine receptors in the regulation of the intestinal immune
response, we induced colitis in CCR2- and CCR5-deficient mice by
continuous oral administration of dextran sodium sulfate (DSS). Both
CCR2- and CCR5-deficient mice were susceptible to DSS-induced
intestinal inflammation. The lack of CCR2 or CCR5 did not reduce the
DSS-induced migration of macrophages into the colonic lamina propria.
However, both CCR5-deficient mice and, to a lesser degree,
CCR2-deficient mice were protected from DSS-induced intestinal
adhesions and mucosal ulcerations. CCR5-deficient mice were
characterized by a greater relative infiltration of CD4+
and NK1.1+ lymphocyte in the colonic lamina propria when
compared to wild-type and CCR2-deficient mice. In CCR5-deficient mice,
mucosal mRNA expression of IL-4, IL-5, and IL-10 was increased, whereas
that of IFN-
was decreased, corresponding to a Th2 pattern of T cell
activation. In CCR2-deficient mice, the infiltration of Th2-type T
cells in the lamina propria was absent, but increased levels of IL-10
and decreased levels of IFN- may have down regulated mucosal
inflammation. Our data indicate that CCR5 may be critical for the
promotion of intestinal Th1-type immune responses in
mice.
This article has been cited by other articles:
|
|
 |
|
  S. Mikami, H. Nakase, S. Yamamoto, Y. Takeda, T. Yoshino, K. Kasahara, S. Ueno, N. Uza, S. Oishi, N. Fujii, et al. Blockade of CXCL12/CXCR4 Axis Ameliorates Murine Experimental Colitis J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 383 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. van Deventer, Q. P. Wu, D. T. Bergstralh, B. K. Davis, B. P. O'Connor, J. P.-Y. Ting, and J. S. Serody C-C Chemokine Receptor 5 on Pulmonary Fibrocytes Facilitates Migration and Promotes Metastasis via Matrix Metalloproteinase 9 Am. J. Pathol., July 1, 2008; 173(1): 253 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Wildenberg, C. G. van Helden-Meeuwsen, J. P. van de Merwe, C. Moreno, H. A. Drexhage, and M. A. Versnel Lack of CCR5 on dendritic cells promotes a proinflammatory environment in submandibular glands of the NOD mouse J. Leukoc. Biol., May 1, 2008; 83(5): 1194 - 1200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Eijkelkamp, C. J Heijnen, A. Lucas, R. T Premont, S. Elsenbruch, M. Schedlowski, and A. Kavelaars G protein-coupled receptor kinase 6 controls chronicity and severity of dextran sodium sulphate-induced colitis in mice Gut, June 1, 2007; 56(6): 847 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Joosten, K. E. van Meijgaarden, N. D. L. Savage, T. de Boer, F. Triebel, A. van der Wal, E. de Heer, M. R. Klein, A. Geluk, and T. H. M. Ottenhoff Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4 PNAS, May 8, 2007; 104(19): 8029 - 8034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Thapa, W. A. Kuziel, and D. J. J. Carr Susceptibility of CCR5-Deficient Mice to Genital Herpes Simplex Virus Type 2 Is Linked to NK Cell Mobilization J. Virol., April 15, 2007; 81(8): 3704 - 3713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Kien, R. Blauwiekel, J. Y. Bunn, T. L. Jetton, W. L. Frankel, and J. J. Holst Cecal Infusion of Butyrate Increases Intestinal Cell Proliferation in Piglets J. Nutr., April 1, 2007; 137(4): 916 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. M. Shah, K. Morimura, and F. J. Gonzalez Expression of peroxisome proliferator-activated receptor-{gamma} in macrophage suppresses experimentally induced colitis Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G657 - G666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Braunersreuther, A. Zernecke, C. Arnaud, E. A. Liehn, S. Steffens, E. Shagdarsuren, K. Bidzhekov, F. Burger, G. Pelli, B. Luckow, et al. Ccr5 But Not Ccr1 Deficiency Reduces Development of Diet-Induced Atherosclerosis in Mice Arterioscler. Thromb. Vasc. Biol., February 1, 2007; 27(2): 373 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. I. Khan, Y. Motomura, H. Wang, R. T. El-Sharkawy, E. F. Verdu, M. Verma-Gandhu, B. J. Rollins, and S. M. Collins Critical role of MCP-1 in the pathogenesis of experimental colitis in the context of immune and enterochromaffin cells Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G803 - G811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zernecke, E. A. Liehn, J.-L. Gao, W. A. Kuziel, P. M. Murphy, and C. Weber Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10 Blood, June 1, 2006; 107(11): 4240 - 4243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Kien, M. Schmitz-Brown, T. Solley, D. Sun, and W. L. Frankel Increased Colonic Luminal Synthesis of Butyric Acid Is Associated with Lowered Colonic Cell Proliferation in Piglets J. Nutr., January 1, 2006; 136(1): 64 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Bonder, M. U. Norman, T. MacRae, P. R. Mangan, C. T. Weaver, D. C. Bullard, D.-M. McCafferty, and P. Kubes P-Selectin Can Support Both Th1 and Th2 Lymphocyte Rolling in the Intestinal Microvasculature Am. J. Pathol., December 1, 2005; 167(6): 1647 - 1660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Terwey, T. D. Kim, A. A. Kochman, V. M. Hubbard, S. Lu, J. L. Zakrzewski, T. Ramirez-Montagut, J. M. Eng, S. J. Muriglan, G. Heller, et al. CCR2 is required for CD8-induced graft-versus-host disease Blood, November 1, 2005; 106(9): 3322 - 3330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Takeuchi, Y. Usui, M. Takeuchi, T. Hattori, T. Kezuka, J. Suzuki, Y. Okunuki, T. Iwasaki, M. Haino, K. Matsushima, et al. CCR5-Deficient Mice Develop Experimental Autoimmune Uveoretinitis in the Context of a Deviant Effector Response Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3753 - 3760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S L-F Pender, V Chance, C V Whiting, M Buckley, M Edwards, R Pettipher, and T T MacDonald Systemic administration of the chemokine macrophage inflammatory protein 1{alpha} exacerbates inflammatory bowel disease in a mouse model Gut, August 1, 2005; 54(8): 1114 - 1120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tokuyama, S. Ueha, M. Kurachi, K. Matsushima, F. Moriyasu, R. S. Blumberg, and K. Kakimi The simultaneous blockade of chemokine receptors CCR2, CCR5 and CXCR3 by a non-peptide chemokine receptor antagonist protects mice from dextran sodium sulfate-mediated colitis Int. Immunol., August 1, 2005; 17(8): 1023 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lugering, M. Floer, S. Westphal, C. Maaser, T. W. Spahn, M. A. Schmidt, W. Domschke, I. R. Williams, and T. Kucharzik Absence of CCR6 Inhibits CD4+ Regulatory T-Cell Development and M-Cell Formation inside Peyer's Patches Am. J. Pathol., June 1, 2005; 166(6): 1647 - 1654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. van Deventer, W. O'Connor Jr., W. J. Brickey, R. M. Aris, J. P.Y. Ting, and J. S. Serody C-C Chemokine Receptor 5 on Stromal Cells Promotes Pulmonary Metastasis Cancer Res., April 15, 2005; 65(8): 3374 - 3379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Yang, I-M. Fang, C.-P. Lin, C.-M. Yang, and M.-S. Chen Effects of the NF-{kappa}B Inhibitor Pyrrolidine Dithiocarbamate on Experimentally Induced Autoimmune Anterior Uveitis Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1339 - 1347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Wang, D. Montufar-Solis, B.-B. Teng, and J. R. Klein Maximum Immunobioactivity of Murine Small Intestinal Intraepithelial Lymphocytes Resides in a Subpopulation of CD43+ T Cells J. Immunol., November 15, 2004; 173(10): 6294 - 6302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S J Connor, N Paraskevopoulos, R Newman, N Cuan, T Hampartzoumian, A R Lloyd, and M C Grimm CCR2 expressing CD4+ T lymphocytes are preferentially recruited to the ileum in Crohn's disease Gut, September 1, 2004; 53(9): 1287 - 1294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Scott Algood and J. L. Flynn CCR5-Deficient Mice Control Mycobacterium tuberculosis Infection despite Increased Pulmonary Lymphocytic Infiltration J. Immunol., September 1, 2004; 173(5): 3287 - 3296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ahlenstiel, R. P. Woitas, J. Rockstroh, and U. Spengler CC-chemokine receptor 5 (CCR5) in hepatitis C--at the crossroads of the antiviral immune response? J. Antimicrob. Chemother., June 1, 2004; 53(6): 895 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Crisman, B. Zhang, L. P. Norman, and J. S. Bond Deletion of the Mouse Meprin {beta} Metalloprotease Gene Diminishes the Ability of Leukocytes to Disseminate through Extracellular Matrix J. Immunol., April 1, 2004; 172(7): 4510 - 4519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Eis, B. Luckow, V. Vielhauer, J. T. Siveke, Y. Linde, S. Segerer, G. P. de Lema, C. D. Cohen, M. Kretzler, M. Mack, et al. Chemokine Receptor CCR1 But Not CCR5 Mediates Leukocyte Recruitment and Subsequent Renal Fibrosis after Unilateral Ureteral Obstruction J. Am. Soc. Nephrol., February 1, 2004; 15(2): 337 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Beck, R. Xavier, J. Wong, I. Ezedi, H. Mashimo, A. Mizoguchi, E. Mizoguchi, A. K. Bhan, and D. K. Podolsky Paradoxical roles of different nitric oxide synthase isoforms in colonic injury Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G137 - G147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Beck, I. M. Rosenberg, R. J. Xavier, T. Koh, J. F. Wong, and D. K. Podolsky Transforming Growth Factor-{beta} Mediates Intestinal Healing and Susceptibility to Injury in Vitro and in Vivo Through Epithelial Cells Am. J. Pathol., February 1, 2003; 162(2): 597 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Krauss-Etschmann, E. Sammler, S. Koletzko, N. Konstantopoulos, D. Aust, B. Gebert, B. Luckow, D. Reinhardt, and D. J. Schendel Chemokine Receptor 5 Expression in Gastric Mucosa of Helicobacter pylori-Infected and Noninfected Children Clin. Vaccine Immunol., January 1, 2003; 10(1): 22 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Spahn, H. Herbst, P. D. Rennert, N. Lugering, C. Maaser, M. Kraft, A. Fontana, H. L. Weiner, W. Domschke, and T. Kucharzik Induction of Colitis in Mice Deficient of Peyer's Patches and Mesenteric Lymph Nodes Is Associated with Increased Disease Severity and Formation of Colonic Lymphoid Patches Am. J. Pathol., December 1, 2002; 161(6): 2273 - 2282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kozaki, W. E. Kaminski, J. Tang, S. Hollenbach, P. Lindahl, C. Sullivan, J.-C. Yu, K. Abe, P. J. Martin, R. Ross, et al. Blockade of Platelet-Derived Growth Factor or Its Receptors Transiently Delays but Does Not Prevent Fibrous Cap Formation in ApoE Null Mice Am. J. Pathol., October 1, 2002; 161(4): 1395 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Abdi, R. N. Smith, L. Makhlouf, N. Najafian, A. D. Luster, H. Auchincloss Jr., and M. H. Sayegh The Role of CC Chemokine Receptor 5 (CCR5) in Islet Allograft Rejection Diabetes, August 1, 2002; 51(8): 2489 - 2495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P V Sivakumar, G M Westrich, S Kanaly, K Garka, T L Born, J M J Derry, and J L Viney Interleukin 18 is a primary mediator of the inflammation associated with dextran sulphate sodium induced colitis: blocking interleukin 18 attenuates intestinal damage Gut, June 1, 2002; 50(6): 812 - 820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mishra, S. P. Hogan, E. B. Brandt, N. Wagner, M. W. Crossman, P. S. Foster, and M. E. Rothenberg Enterocyte Expression of the Eotaxin and Interleukin-5 Transgenes Induces Compartmentalized Dysregulation of Eosinophil Trafficking J. Biol. Chem., February 1, 2002; 277(6): 4406 - 4412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Reardon, A. Sanchez, C. M. Hogaboam, and D. M. McKay Tapeworm Infection Reduces Epithelial Ion Transport Abnormalities in Murine Dextran Sulfate Sodium-Induced Colitis Infect. Immun., July 1, 2001; 69(7): 4417 - 4423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mack, J. Cihak, C. Simonis, B. Luckow, A. E. I. Proudfoot, H. Bruhl, M. Frink, H.-J. Anders, V. Vielhauer, J. Pfirstinger, et al. Expression and Characterization of the Chemokine Receptors CCR2 and CCR5 in Mice J. Immunol., April 1, 2001; 166(7): 4697 - 4704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. Ajuebor, C. M. Hogaboam, S. L. Kunkel, A. E. I. Proudfoot, and J. L. Wallace The Chemokine RANTES Is a Crucial Mediator of the Progression from Acute to Chronic Colitis in the Rat J. Immunol., January 1, 2001; 166(1): 552 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nishiyama, T. Sakaguchi, T. Kinugasa, X. Gu, R. P. MacDermott, D. K. Podolsky, and H.-C. Reinecker Interleukin-2 Receptor beta Subunit-dependent and -independent Regulation of Intestinal Epithelial Tight Junctions J. Biol. Chem., September 14, 2001; 276(38): 35571 - 35580. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
