HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/G1089    most recent 00571.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moreno, C. Articles by Devière, J. Search for Related Content PubMed PubMed Citation Articles by Moreno, C. Articles by Devière, J.

INFLAMMATION/IMMUNITY/MEDIATORS

Chemokine receptor CCR5 deficiency exacerbates cerulein-induced acute pancreatitis in mice

¹Division of Gastroenterology and Hepatopancreatology, Erasme Hospital; ²Laboratory of Experimental Gastroenterology, Free University of Brussels; ³Division of Pathology, Erasme Hospital; and ⁴Institute of Interdisciplinary Research, Free University of Brussels, Brussels, Belgium

Submitted 19 December 2005 ; accepted in final form 1 August 2006

Acute pancreatitis (AP) is an inflammatory disease involving the production of different cytokines and chemokines and is characterized by leukocyte infiltration. Because the chemokine receptor CCR5 and its ligands [the CC chemokines CCL3/MIP-1, CCL4/MIP-1, and CCL5/regulated upon activation, normal T cell expressed and secreted (RANTES)] regulate leukocyte chemotaxis and activation, we investigated the expression of CCR5 ligands and the role of CCR5 and its ligands in experimental AP in mice. AP was induced by hourly intraperitoneal injections of cerulein in CCR5-deficient (CCR5^–/–) or wild-type (WT) mice. Induction of AP by cerulein resulted in an early increase of pancreatic CCL2, CCL3, and CCL4 mRNA expression, whereas CCL5 mRNA expression occurred later. CCR5^–/– mice developed a more severe pancreatic injury than WT mice during cerulein-induced AP, as assessed by a more pronounced increase in serum amylase and lipase levels and by more severe pancreatic edema, inflammatory infiltrates (mainly neutrophils), and necrosis. CCR5^–/– mice also exhibited increased production of CCL2/MCP-1, CCL3/MIP-1, and CCL4/MIP-1 during the course of cerulein-induced AP. In vivo simultaneous neutralization of CC chemokines with monoclonal antibodies in CCR5^–/– mice reduced the severity of cerulein-induced AP, indicating a role of CC chemokines in exacerbating the course of AP in the absence of CCR5. Moreover, simultaneous neutralization of CCR5 ligands in WT mice also reduced the severity of cerulein-induced AP. In conclusion, lack of the chemokine receptor CCR5 exacerbates experimental cerulein-induced AP and leads to increased levels of CC chemokines and a more pronounced pancreatic inflammatory infiltrate, suggesting that CCR5 expression can modulate severity of AP.

This article has been cited by other articles:

				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]