Actin polymerization induces shedding of FcgammaRIIIb (CD16) from human neutrophils.
FcgammaRIIIb (CD16) is a glycosyl phosphatidylinositol (GPI)-anchored low-affinity IgG receptor, exclusively expressed on human neutrophils. FcgammaRIIIb associates with complement receptor 3 (CR3, Mac-1, CD11b/CD18), which may indirectly link FcgammaRIIIb to the actin cytoskeleton. Upon neutrophil activation, apoptosis, or chemotaxis, FcgammaRIIIb is shed from the cell surface. In all of these events, actin rearrangements play an important role. To establish a role for the actin cytoskeleton in the control of FcgammaRIIIb shedding, we treated human neutrophils with jasplakinolide, an actin-polymerizing peptide. We show that enhanced actin polymerization induces time- and dose-dependent shedding of FcgammaRIIIb. This effect was not restricted to FcgammaRIIIb, because the cell surface expression of CD43, CD44, and L-selectin was also downregulated after induction of actin polymerization. This actin-dependent pathway is staurosporine sensitive but does not appear to involve activation of PKC or CR3. These data show that the actin cytoskeleton can regulate protein ectodomain shedding from human neutrophils.
Laboratory for Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
P J
PJ
Middelhoven
J D
JD
van Buul
M
M
Kleijer
D
D
Roos
P L
PL
Hordijk
D000199:Actins / Q000378:metabolism*; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules; D003599:Cytoskeleton / Q000378:metabolism; D047630:Depsipeptides; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007700:Kinetics; D019041:L-Selectin / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D051917:Leukosialin; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology
D000199:Actins; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D047630:Depsipeptides; D018960:Hyaluronan Receptors; D051917:Leukosialin; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D010456:Peptides, Cyclic; D017452:Receptors, IgG; C465014:SPN protein, human; D012795:Sialoglycoproteins; C057531:jasplakinolide; D019041:L-Selectin; D011494:Protein Kinases; D007781:Lactoferrin; D019311:Staurosporine