Platelet-associated IgAs and impaired GPVI responses in platelets lacking WIP. Blood 2009 Nov 19;114(21):4729-37
Date
08/21/2009Pubmed ID
19692704Pubmed Central ID
PMC2780308DOI
10.1182/blood-2009-02-202721Scopus ID
2-s2.0-73949146436 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
The role of the Wiskott-Aldrich syndrome protein (WASp) in platelet function is unclear because platelets that lack WASp function normally. WASp constitutively associates with WASp-interacting protein (WIP) in resting and activated platelets. The role of WIP in platelet function was investigated using mice that lack WIP or WASp. WIP knockout (KO) platelets lack WASp and thus are double deficient. WIP KO mice have a thrombocytopenia, similar to WASp KO mice, resulting in part from enhanced platelet clearance. Most WIP KO, but not WASp KO, mice evolved platelet-associated immunoglobulins (Ig) of the IgA class, which normalize their platelet survival but diminish their glycoprotein VI (GPVI) responses. Protein tyrosine phosphorylation, including that of phospholipase C-gamma2, and calcium mobilization are impaired in IgA-presenting WIP KO platelets stimulated through GPVI, resulting in defects in alpha-granule secretion, integrin alphaIIbbeta3 activation, and actin assembly. The anti-GPVI antibody JAQ1 induces the irreversible loss of GPVI from circulating platelets in wild-type mice, but not in WIP KO mice that bear high levels of platelet-associated IgAs. Together, the data indicate that platelet-associated IgAs negatively modulate GPVI signaling and function in WIP KO mice.
Author List
Falet H, Marchetti MP, Hoffmeister KM, Massaad MJ, Geha RS, Hartwig JHAuthors
Herve Falet PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinKarin Hoffmeister MD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBlood Platelets
Blotting, Western
Carrier Proteins
Cytoskeletal Proteins
Electrophoresis, Polyacrylamide Gel
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Immunoglobulin A
Mice
Mice, Knockout
Platelet Membrane Glycoproteins
Signal Transduction
Thrombocytopenia
Wiskott-Aldrich Syndrome Protein
