CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B4 (LTB4). CYP4F18 has an unusual expression\nin neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wild type\nand Cyp4f18 knockout neutrophils using an in vitro assay. There was no significant difference in the chemotactic response\nto LTB4, but the response to complement component C5a increased 1.9ââ?¬â??2.25-fold in knockout cells compared to wild-type (P <\n0.01). This increase was still observed when neutrophils were treated with inhibitors of eicosanoid synthesis. There were no changes\nin expression of other CYP4 enzymes in knockout neutrophils that might compensate for loss of CYP4F18 or lead to differences\nin activity. A mouse model of dextran sodium sulfate colitis was used to investigate the consequences of increased C5a-dependent\nchemotaxis in vivo, but there was no significant difference in weight loss, disease activity, or colonic tissue my eloper oxidase between\nwild-type and Cyp4f18 knockout mice. This study demonstrates the limitations of inferring CYP4F function based on an ability to\nuse LTB4 as a substrate, points to expanding roles for CYP4F enzymes in immune regulation, and underscores the in vivo challenges\nof CYP knockout studies.
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