Role of CCR2 in macrophage migration into the liver during acetaminophen-induced hepatotoxicity in the mouse Export

@article{Dambach:2002p437, abstract = {The biological effects of monocyte chemoattractant protein (MCP) 1 are mediated by binding to C-C chemokine receptor (CCR) 2. In the present studies, we used CCR2 knockout (CCR2-/-) mice to examine the role of MCP-1 in acetaminophen-induced macrophage accumulation in the liver, expression of inflammatory cytokines, and hepatotoxicity. We found that hepatic expression of CCR2 and MCP-1 was increased 10-fold and 20-fold, respectively, 12 to 72 hours after administration of acetaminophen to wild-type mice. Expression of these proteins was localized in centrilobular regions of the liver. Whereas MCP-1 was expressed by both hepatocytes and macrophages, CCR2 was identified in inflammatory macrophages. F4/80 is a marker of mature macrophages expressed in large quantities by Kupffer cells. In wild-type mice, a 75\% decrease in F4/80-positive macrophages was observed 24 to 48 hours after administration of acetaminophen. In contrast, expression of macrosialin (CD68), a marker of activated macrophages, increased 2-fold 24 to 72 hours after administration of acetaminophen and was associated with inflammatory cells. Although there was a decrease in the overall severity of inflammation and in the number of macrosialin-positive macrophages 72 hours after administration of acetaminophen in CCR2-/- mice, the number of F4/80-positive cells did not change. Loss of CCR2 was also found to alter acetaminophen-induced expression of tumor necrosis factor alpha, monocyte chemoattractant protein 3, and KC/gro. However, the overall outcome of acetaminophen-induced hepatic injury was not affected. In conclusion, these data indicate that MCP-1 and CCR2 contribute to the recruitment of a subset of activated macrophages into the liver during acetaminophen-induced hepatotoxicity that may be important in resolution of tissue injury.}, author = {Dambach, Donna M. and Watson, Linda M. and Gray, Kevin R. and Durham, Stephen K. and Laskin, Debra L.}, citeulike-article-id = {3046167}, citeulike-linkout-0 = {http://www3.interscience.wiley.com/journal/106597667/abstract?CRETRY=1&SRETRY=0}, citeulike-linkout-1 = {http://dx.doi.org/10.1053/jhep.2002.33162}, doi = {10.1053/jhep.2002.33162}, journal = {Hepatology}, keywords = {acetaminophen, analgesics, animals, c57bl, ccl2, ccr2, cell, chemokine, expression, factor-alpha, file-import-08-07-27, gene, icr, inbred, interleukin-1, knockout, liver, macrophages, male, mice, movement, necrosis, non-narcotic, receptors, tumor}, local-url = {file://localhost/Users/ken/Documents/Papers/2002/Dambach/Hepatology\%202002\%20Dambach.pdf}, month = {May}, number = {5}, pages = {1093--103}, posted-at = {2008-07-27 14:45:53}, priority = {2}, title = {Role of CCR2 in macrophage migration into the liver during acetaminophen-induced hepatotoxicity in the mouse}, url = {http://dx.doi.org/10.1053/jhep.2002.33162}, volume = {35}, year = {2002} }

TY - JOUR ID - Dambach:2002p437 L3 - citeulike-article-id:3046167 N2 - The biological effects of monocyte chemoattractant protein (MCP) 1 are mediated by binding to C-C chemokine receptor (CCR) 2. In the present studies, we used CCR2 knockout (CCR2-/-) mice to examine the role of MCP-1 in acetaminophen-induced macrophage accumulation in the liver, expression of inflammatory cytokines, and hepatotoxicity. We found that hepatic expression of CCR2 and MCP-1 was increased 10-fold and 20-fold, respectively, 12 to 72 hours after administration of acetaminophen to wild-type mice. Expression of these proteins was localized in centrilobular regions of the liver. Whereas MCP-1 was expressed by both hepatocytes and macrophages, CCR2 was identified in inflammatory macrophages. F4/80 is a marker of mature macrophages expressed in large quantities by Kupffer cells. In wild-type mice, a 75% decrease in F4/80-positive macrophages was observed 24 to 48 hours after administration of acetaminophen. In contrast, expression of macrosialin (CD68), a marker of activated macrophages, increased 2-fold 24 to 72 hours after administration of acetaminophen and was associated with inflammatory cells. Although there was a decrease in the overall severity of inflammation and in the number of macrosialin-positive macrophages 72 hours after administration of acetaminophen in CCR2-/- mice, the number of F4/80-positive cells did not change. Loss of CCR2 was also found to alter acetaminophen-induced expression of tumor necrosis factor alpha, monocyte chemoattractant protein 3, and KC/gro. However, the overall outcome of acetaminophen-induced hepatic injury was not affected. In conclusion, these data indicate that MCP-1 and CCR2 contribute to the recruitment of a subset of activated macrophages into the liver during acetaminophen-induced hepatotoxicity that may be important in resolution of tissue injury. IS - 5 JF - Hepatology EP - 103 TI - Role of CCR2 in macrophage migration into the liver during acetaminophen-induced hepatotoxicity in the mouse VL - 35 SP - 1093 KW - acetaminophen KW - analgesics KW - animals KW - c57bl KW - ccl2 KW - ccr2 KW - cell KW - chemokine KW - expression KW - factor-alpha KW - file-import-08-07-27 KW - gene KW - icr KW - inbred KW - interleukin-1 KW - knockout KW - liver KW - macrophages KW - male KW - mice KW - movement KW - necrosis KW - non-narcotic KW - receptors KW - tumor AU - Dambach, Donna AU - Watson, Linda AU - Gray, Kevin AU - Durham, Stephen AU - Laskin, Debra PY - 2002/May// UR - http://dx.doi.org/10.1053/jhep.2002.33162 ER -