Objective— To determine the role of CXCR2, the receptor for cysteine-X-cysteine (CXC) chemokines, and its primary effector cell, the neutrophil (PMN), on deep venous thrombosis (DVT) resolution.

Methods and Results— DVT in BALB/c, anti-CXCR2 antibody-treated, and BALB/c CXCR2^−/− mice were created by infrarenal inferior vena cava (IVC) ligation and the thrombus harvested at various time points over 21 days. The CXCR2^−/− mice had significantly larger thrombi at early time points (days 2 to 8), and significantly decreased intrathrombus PMNs, monocytes, and neovascularization as compared with controls. Thrombus KC/CXCL1 was significantly higher at 2 days in CXCR2^−/− thrombi as measured by enzyme-linked immunosorbent assay. Fibrin content was significantly higher, with less uPA gene expression at 4 days in CXCR2^−/− thrombi. Late fibrotic maturation of the thrombus was delayed in the CXCR2^−/− mice, with significantly decreased 8 day MMP-2 activity, whereas MMP-9 activity was elevated as compared with controls. Similar impairment in DVT resolution was found at 8 days with anti-CXCR2 inhibition. However, systemic neutropenia, unlike CXCR2 deletion, did not increase the thrombus size as compared with controls.

Conclusions— Normal DVT resolution involves CXCR2-mediated neovascularization, collagen turnover, and fibrinolysis, and it is probably primarily monocyte-dependent.