Inhibition of Prostaglandin by Selective Cyclooxygenase 2 Inhibitors Accounts for Reduced Rat Leukocyte Migration

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• 作者：Gustavo Batista de Menezes ; Webster Glayser Pimenta dos Reis ; J¨²lia Maria Moreira Santos ; Igor Dimitri Gama Duarte and Janetti Nogueira de Francischi
• 关键词：coxibs ; cyclooxygenases ; inflammation ; leukocyte ; prostaglandin \textF2a {\text{F}}_{{2\alpha }}
• 刊名：Inflammation
• 出版年：2005
• 出版时间：December, 2005
• 年：2005
• 卷：29
• 期：4-6
• 页码：163-169
• 全文大小：332 KB

文摘

To investigate whether selective COX 2 inhibitors (celecoxib, rofecoxib) would play a role in a model of leukocyte migration in rats. Bacterial endotoxin (Escherichia coli LPS) was intraperitoneally injected at time zero in rats that were previously treated with unspecific and selective cyclooxygenase inhibitors. LPS induced a dose and time-dependent increase in leukocyte number, which was predominantly related to the presence of PMN neutrophils. Only rats treated with selective COX 2 inhibitors and indomethacin showed a significant reduction in leukocyte numbers following LPS administration. Prostaglandins E₂ and \textF_2a {\text{F}}_{{2\alpha }} were injected into the peritoneum and the chemoatractant effect was studied. Only \textPGF_2a {\text{PGF}}_{{2\alpha }} was able to induce neutrophil increase following injection. Intraperitoneal reposition of \textPGF_2a {\text{PGF}}_{{2\alpha }} restored the abrogated leukocyte response to LPS, shown by rats pretreated with rofecoxib. It can be concluded that COX 2, through \textPGF_2a {\text{PGF}}_{{2\alpha }} release, is the isoform responsible for neutrophil recruitment in the rat model of LPS-induced inflammation.