CD47 contributes to neutrophil recruitment (146.2)

Resumen

Leukocyte recruitment plays a key role in an inflammatory response. CD47 associates “in cis” with β1, β2 and β3 integrins. CD47 also interacts “in trans” with Signal Regulatory Proteins (SIRP-α and -γ) and thrombospondin (TSP). CD47 plays an important but incompletely understood role in the innate and adaptive immune responses. Neutrophil recruitment in CD47KO mice is reduced in models of peritonitis, lung injury and dermal air pouch inflammation, but the exact contribution(s) of CD47 to neutrophil (PMN) extravasation is unclear. Here we report that in the TNF-α-stimulated cremaster muscle microcirculation, PMN rolling velocity is elevated compared to WT (17.8±1.5μm/s vs. 14.3±1.0μm/s, respectively; p<0.05), whereas there was no difference between WT and CD47KO mice in CXCL1-induced arrest. Also, PMN transendothelial migration (TEM) is reduced by 30% in CD47KO mice compared to WT mice (p<0.05). In vitro flow chamber assays demonstrate reduced adhesion (30% reduction vs. WT; p<0.05) and TEM (60% reduction vs. WT; p<0.05) of CD47KO PMN compared to WT PMN across WT TNF-activated murine endothelium. We have previously reported that CD47 physically interacts with β2 integrins and regulates integrin affinity on T cells (Azcutia et al., Mol Biol Cell 2013). These previous observations and our current results suggest that CD47 plays a role in PMN recruitment through the regulation of β2 integrin adhesive function.