CD47 deficiency does not impede polymorphonuclear neutrophil transmigration but attenuates granulopoiesis at the postacute stage of colitis.

Previous studies have suggested that CD47, an essential cell-surface protein, plays an important role in polymorphonuclear neutrophil (PMN) transmigration across tissue cells and extracellular matrix. In the current study, the role of CD47 in PMN transmigration and infiltration into tissues was further evaluated by investigating the function of CD47(-/-) PMN and inflammatory conditions induced in CD47(-/-) mice. Using in vitro time-course assays, we found that CD47(-/-) PMN exhibited no impediment, but slightly enhanced response to and transmigration toward, the chemoattractant fMLF. In vivo analysis in CD47(-/-) mice by inducing acute peritonitis and aggressive colitis observed consistent results, indicating that both PMN and monocytes effectively infiltrated inflammatory sites despite the absence of CD47 on these leukocytes or the surrounding tissue cells. Although PMN transmigration was not delayed in CD47(-/-) mice, fewer PMN were found in the intestine at the postacute/chronic stage of chronic colitis induced with sustained low-dose dextran sulfate sodium. Further analysis suggested that the paucity of PMN accumulation was attributable to attenuated granulopoiesis secondary to assessed lower levels of IL-17. Administration of exogenous IL-17A markedly increased PMN availability and rapidly rendered severe colitis in CD47(-/-) mice under dextran sulfate sodium treatment.