Abstract
Signaling through the inhibitory receptor signal regulatory protein-alpha (SIRPα) controls effector functions in phagocytes. However, there are also indications that interactions between SIRPα and its ligand CD47 are involved in phagocyte transendothelial migration. We have investigated the involvement of SIRPα signaling in phagocyte migration in vitro and in vivo using mice that lack the SIRPα cytoplasmic tail. During thioglycolate-induced peritonitis in SIRPα mutant mice, both neutrophil and macrophage influx were found to occur, but to be significantly delayed. SIRPα signaling appeared to be essential for an optimal transendothelial migration and chemotaxis, and for the amoeboid type of phagocyte migration in 3-dimensional environments. These findings demonstrate, for the first time, that SIRPα signaling can directly control phagocyte migration, and this may contribute to the impaired inflammatory phenotype that has been observed in the absence of SIRPα signaling.
Highlights
Phagocytes, including granulocytes and macrophages, play a central role during local inflammation, triggered by infection or by other causes, such as e.g. autoimmunity
In line with studies previously reported [17,18] phagocyte immigration in wild type (WT) mice occurs in two consecutive waves, which involves first an early influx of predominantly neutrophils peaking at 4 h doi:10.1371/journal.pone.0127178.g001
There were no significant differences in the blood cell counts of neutrophils and monocytes before and during the experiment (S1A Fig) that could have contributed to the observed delay in phagocyte recruitment and the expression levels of some of the most important integrins for leukocyte extravasation on neutrophils and peripherial blood mononucleated cells (PBMCs) of WT and SIRPαΔcyt showed no difference (S1B Fig)
Summary
Phagocytes, including granulocytes and macrophages, play a central role during local inflammation, triggered by infection or by other causes, such as e.g. autoimmunity. Our in vitro experiments demonstrated that the amoeboid but not the mesenchymal mode of interstitial migration of macrophages was impaired in the absence of SIRPα signaling. To investigate a role for SIRPα signaling in phagocyte migration in-vivo we subjected mice lacking the SIRPα cytoplasmic tail (designated SIRPαΔcyt)[15] to an acute thioglycollate-induced sterile peritoneal inflammation.
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