|Budget Amount *help
¥16,420,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2007: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2006: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2005: ¥6,300,000 (Direct Cost: ¥6,300,000)
Integrin αIIb, a well-known marker of megakaryocyte-platelet lineage, has been recently recognized on hemopoietic progenitors. We now demonstrate that integrin αIIb is highly expressed on mouse and human mast cells including mouse bone marrow-derived mast cells, peritoneal mast cells, and human cord blood-derived mast cells, and that its binding to extracellular matrix proteins leads to enhancement of biological functions of mast cells in concert with various stimuli. With exposure to various stimuli, including cross-linking of FcεRI and stem cell factor, mast cells adhered to extracellular matrix proteins such as fibrinogen and von Willebrand factor in an integrin αIIb-dependent manner. In addition, the binding of mast cells to fibrinogen enhanced proliferation, cytokine production, and migration and induced uptake of soluble fibrinogen in response to stem cell factor stimulation, implicating integrin αIIb in a variety of mast cell functions. In conclusion, mouse and human mast cells express functional integrin αIIb.
Analysis of integrin αIIb-deficient mouse delineated that integrin αIIb competed with integrin αV in associating with integrin β3 in mast cells and that mast cells-associated allergic responses were attenuated by integrin αIIb deficiency. In addition, the number of mast cells in the skin of the back, but not ear, was decreased in integrin αIIb-deficient mouse as compared with wild type mouse. Collectively, integrin αIIbβ3 might be involved in the distribution and function of mast cells, although the effect of enhanced expression levels of integrin αVβ3 in the absence of integrin αIIb must be considered. Further examination is necessary to completely understand the in vivo function of integrin αIIb, leading to new therapeutic approaches forthcoming for mast cell-mediated diseases.