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However, precise control of the inflammatory response prevents overshooting reactions. Neutrophil activation initiates signaling, resulting in integrin \u03b22 (Itgb2) activation and neutrophil arrest. Src family kinases are involved in multiple cellular processes and are negatively regulated by the C-terminal Src kinase (Csk). During this study, we investigated the mechanism by which Csk regulates integrin activation and neutrophil recruitment. Here, we demonstrated that Csk deficiency in murine neutrophils resulted in increased neutrophil adhesion to the endothelium along with decreased neutrophil transmigration into inflamed tissues compared with their littermate controls. In bacterial pneumonia, infected\n                    <jats:italic>Csk<\/jats:italic>\n                    -deficient mice showed higher bacterial burdens and decreased neutrophil recruitment, while other immune cell counts and cytokine levels were not significantly different compared to control. Analyses of\n                    <jats:italic>Csk<\/jats:italic>\n                    -deficient neutrophils revealed an increased Itgb2 affinity, leading to reduced migration and intravascular crawling. Mechanistically, elevated cAMP levels increased protein kinase A activity, which subsequently enhanced Csk activation. Csk, in turn, suppressed Src family kinase activation through phosphorylation (Y529). 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