Myeloid-Speciric Deletion Of CXCR4 Enhanced Recovery In A Murine Hindlimb Ischemia Model

Background and ObjectiveMyeloid cells play important roles in patients with occlusive vascular disease. SDF-1/CXCR4 is a key chemotaxis for leukocyte recruitment. However, the role of SDF-1/CXCR4 axis in ischemic induced inflammatory cells infiltration is remain unclear. This study is designed to investigate whether SDF-1/CXCR4 participate in myeloid cell engraftment after hindlimb ischemia, and explored the mechanism by which SDF-1/CXCR4 might regulate myeloid cells pro-angiogenic and pro-inflammatory functions.MethodsWe generated myeloid cell-specific CXCR4 knockout mice by Cre-LoxP technology. Mice critical limb ischemia model were induced by femoral artery ligation. Mice ischemic muscle were harvested 1,3,7,14 days after surgery, and leukocytes infiltration was examined by immunofluorescence and flow cytometry. Ishchmic limb blood perfusion recover was measured by laser Doppler Proinflammatory cytokine protein levels in ischemic tissue were measured by q-PCR assay.ResultsMyeloid CXCR4 deficient mice exhibited promoted blood reperfusion and improved limb salvage compared with control mice. The mRNA level of inflammatory cytokines and neutrophil counts were increased in ischemic muscle of MKO mice, indicating augmented inflammatory response. CXCR4 deletion led to promote macrophage polarization toward pro-inflammatory phenotype but not anti-inflammatory phenotype.ConclusionsThese results suggested that SDF-1/CXCR4 axis is crucial for myeloid cells infiltration and inflammatory regulation. Elucidating the mechanism responsible for myeloid cells engraftment and contribution of myeloid cells to angiogenesis is of clinical relevant in the quest to find new therapeutic target of ischemic diseases.