BACKGROUND: Ca METHODS: Myeloid-specific Cracr2a conditional knockout mice and intravital microscopy were used to investigate the physiologic role of neutrophil Cracr2a in neutrophil recruitment in vascular inflammation. Cracr2a-deficient neutrophils or dHL-60 (differentiated human promyelocytic leukemia) cells and Cracr2a-derived peptides were used in flow cytometry, immunoprecipitation, cytosolic Ca RESULTS: Compared with wild-type control mice, Cracr2a conditional knockout mice exhibited significantly reduced adhesion, crawling, and transmigration of neutrophils on ear and cremaster venules in tumor necrosis factor-α-induced sterile inflammation. Neutrophil Cracr2a rapidly interacts with Stim1 (stromal interaction molecule 1) after agonist stimulation and facilitates Ca CONCLUSIONS: Our results demonstrate that neutrophil CRACR2A promotes neutrophil recruitment to sites of sterile inflammation, such as ischemic stroke. Blocking the STIM1-CRACR2A interaction may be a novel therapeutic strategy to mitigate inflammation and consequent tissue injury.