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(Journal of Leukocyte Biology. 2001;70:801-811.)
© 2001 by Society for Leukocyte Biology

Role of Src kinases and Syk in Fc receptor-mediated phagocytosis and phagosome-lysosome fusion

Meytham Majeed^*, Elena Caveggion^*, Clifford A. Lowell and Giorgio Berton^*

^* Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy, and
Department of Laboratory Medicine, University of California San Francisco, San Francisco

Correspondence: Meytham Majeed, Ph.D., Department of Health and Environment, Division of Medical Microbiology, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. E-mail: meyma{at}ihm.liu.se

Phagocytosis is increased by Fc receptors (FcRs), and studies with syk^-/- macrophages demonstrated that Syk kinase is required for FcR phagocytosis. Similar studies with macrophages lacking the Src family kinases Hck, Fgr, and Lyn showed that these kinases are not required for phagocytosis but that they enhance the rate of particle engulfment. In this report we show that both wild-type and hck^-/-fgr^-/- macrophages expressed Fyn, Src, and Yes and that these kinases were activated on ingestion of immunoglobulin G (IgG)-coated particles and redistributed, together with Syk, to actin-rich phagocytic cups and the phagosomal membrane. At doses blocking IgG-dependent phagocytosis, the tyrosine kinase inhibitors PP1 and piceatannol inhibited both Src family kinase and Syk activities, as well as their redistribution to actin-rich phagocytic cups. Hck, Fgr, and Lyn were dispensable for lysosome-phagosome fusion (PLF) induced by IgG-coated particles. However, PP1 or piceatannol hampered unopsonized yeast-induced PLF despite the fact that they did not block yeast internalization.

Key Words: protein tyrosine phosphorylation • immune receptors • signal transduction • Fyn • Yes

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