Departmental Papers (CBE)
Document Type
Journal Article
Date of this Version
March 2008
Abstract
Phagocytosis of foreign cells or particles by macrophages is a rapid process that is inefficient when faced with "self" cells that display CD47—although signaling mechanisms in self-recognition have remained largely unknown. With human macrophages, we show the phagocytic synapse at cell contacts involves a basal level of actin-driven phagocytosis that, in the absence of species-specific CD47 signaling, is made more efficient by phospho-activated myosin. We use "foreign" sheep red blood cells (RBCs) together with CD47-blocked, antibody-opsonized human RBCs in order to visualize synaptic accumulation of phosphotyrosine, paxillin, F-actin, and the major motor isoform, nonmuscle myosin-IIA. When CD47 is functional, the macrophage counter-receptor and phosphatase-activator SIRPα localizes to the synapse, suppressing accumulation of phosphotyrosine and myosin without affecting F-actin. On both RBCs and microbeads, human CD47 potently inhibits phagocytosis as does direct inhibition of myosin. CD47–SIRPα interaction initiates a dephosphorylation cascade directed in part at phosphotyrosine in myosin. A point mutation turns off this motor's contribution to phagocytosis, suggesting that self-recognition inhibits contractile engulfment.
Recommended Citation
Tsai, R. K., & Discher, D. E. (2008). Inhibition of "self" engulfment through deactivation of myosin-II at the phagocytic synapse between human cells. Retrieved from https://repository.upenn.edu/cbe_papers/108
Date Posted: 20 March 2008
This document has been peer reviewed.
Comments
Copyright The Rockefeller University Press. This research was originally published in The Journal of Cell Biology, Volume 180, Issue 5, March 2008, pages 989-1003.
Publisher URL: http://dx.doi.org/10.1083/jcb.200708043