Fcgamma receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn.
Macrophage Fcgamma receptors (FcgammaRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined FcgammaR 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 FcgammaR-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 FcgammaR-mediated phagocytosis, one involving initiation of actin polymerization and the second involving activation of Syk and subsequent internalization. Since FcgammaR-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.
Fitzer-Attas
C J
CJ
Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143, USA.
Lowry
M
M
Crowley
M T
MT
Finn
A J
AJ
Meng
F
F
DeFranco
A L
AL
Lowell
C A
CA
D000199:Actins / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010587:Phagocytosis / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D051572:Proto-Oncogene Proteins c-hck; D011961:Receptors, Fc / Q000502:physiology*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D011518:Proto-Oncogene Proteins; D011961:Receptors, Fc; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; C496632:Hck protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D051572:Proto-Oncogene Proteins c-hck; D019061:src-Family Kinases