Premium
The role of VAV guanine nucleotide exchange factor in Dectin‐1 mediated phagocytosis
Author(s) -
Johnstone Jill Kathleen,
Morin Nicole A,
Cioffi William G,
Reichner Jonathan S
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.929.5
Subject(s) - phagocytosis , opsonin , microbiology and biotechnology , intracellular , guanine nucleotide exchange factor , receptor , actin cytoskeleton , macrophage , biology , signal transduction , chemistry , cytoskeleton , cell , biochemistry , in vitro
Phagocytosis involves the cellular recognition and engulfment of foreign particles by a diverse number of cell surface receptors on phagocytes. Particle recognition by phagocytic receptors is accompanied by polymerization of the actin cytoskeleton, which has regulatory pathways that are complex and may be receptor dependent. VAV is a guanine nucleotide exchange factor (GEF) that regulates RhoGTPases, which in turn regulate cytoskeleton rearrangement. We tested the hypothesis that in peritoneal macrophages, VAV GEFs are essential for Dectin‐mediated phagocytosis, and are not needed for Fc‐mediated phagocytosis. Peritoneal macrophages were obtained from wild type (WT) and VAV‐knockout mice by peritoneal lavage, and were assayed for phagocytosis of zymocel (Dectin‐1 dependent), and IgG opsonized latex beads (FcR‐dependent) for 30 minutes at 37oC. Intracellular particles were then enumerated per 100 cells. In the Dectin‐1 phagocytic assay, VAV‐knockout macrophages ingested fewer zymocel particles than WT macrophages (p<0.05). In the Fc‐mediated phagocytic assay, VAV‐knock‐out macrophages ingested a similar amount of IgG‐opsonized latex beads as WT (p>0.05). These findings are the first demonstration for the role of VAV in Dectin‐1 mediated phagocytosis and further define the complex regulation of phagocytosis by highlighting a receptor‐specific intracellular signaling mechanism.