Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 439K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fitzer-Attas, C. J. Articles by Lowell, C. A. Search for Related Content PubMed PubMed Citation Articles by Fitzer-Attas, C. J. Articles by Lowell, C. A. Social Bookmarking                            What's this?

Original Article

Fc Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn

^a From the Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143
^b From the George Williams Hooper Foundation, University of California at San Francisco, San Francisco, California 94143
^c From the Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California 94143
Department of Laboratory Medicine, University of California at San Francisco, 513 Parnassus Ave., San Francisco, CA 94143.415-502-6497415-476-2963

clowell{at}cgl.ucsf.edu

Macrophage Fc receptors (FcRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined FcR signaling and phagocytic function in bone marrow–derived macrophages from mutant mice lacking the major Src family kinases expressed in these cells, Hck, Fgr, and Lyn. Many FcR-induced functional responses and signaling events were diminished or delayed in these macrophages, including immunoglobulin (Ig)G-coated erythrocyte phagocytosis, respiratory burst, actin cup formation, and activation of Syk, phosphatidylinositol 3-kinase, and extracellular signal–regulated kinases 1 and 2. Significant reduction of IgG-dependent phagocytosis was not seen in hck^–/–fgr^–/– or lyn^–/– cells, although the single mutant lyn^–/– macrophages did manifest signaling defects. Thus, Src family kinases clearly have roles in two events leading to FcR-mediated phagocytosis, one involving initiation of actin polymerization and the second involving activation of Syk and subsequent internalization. Since FcR-mediated phagocytosis did occur at modest levels in a delayed fashion in triple mutant macrophages, these Src family kinases are not absolutely required for uptake of IgG-opsonized particles.

Key Words: actin polymerization • Fc receptors • macrophage • phagocytosis • Src family kinases

Abbreviations used in this paper: EA, IgG-coated sheep erythrocyte; Erk, extracellular signal–regulated kinase; GST, glutathione S-transferase; ITAM, immunoreceptor tyrosine-based activation motif; JNK, c-Jun NH₂-terminal kinase; LCM, L cell–conditioned medium; MAP, mitogen-activated protein; PI 3-kinase, phosphatidylinositol 3-kinase; SH2, Src homology 2.

© 2000 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS