1. Evidence That Integrin αllbβ3-dependent Interaction of Mast Cells with Fibrinogen Exacerbates Chronic lnflammation.
- Author
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Oki, Toshihiko, Eto, Koji, lzawa, Kumi, Yamanishi, Yoshinori, Inagaki, Naoki, Frampton, Jon, Kitamura, Toshio, and Kitaura, Jiro
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MAST cells , *INTEGRINS , *MEGAKARYOCYTES , *BONE marrow cells , *CELL proliferation , *CYTOKINES , *IMMUNE response , *STAPHYLOCOCCUS aureus - Abstract
Integrin αIIbβ3 is expressed in mast cells as well as in megakaryocytes/platelets. A recent study has shown that surface expression levels of integrin αVβ3 are elevated in integrin αIIb-deficient bone marrow-derived mast cells (BMMCs) as compared with wild-type (WT) counterparts, but the underlying mechanism remains obscure. Here we demonstrate by transducing integrin αllb into integrin αIIb-deficient BMMCs that surface expression levels of integrin αVβ3 are inversely related to those of integrin αIIbβ3. Thus, competitive association of integrin β3 with integrin αllb or integrin αV determines surface expression levels of integrin αIIbβ3 or αVβ3 in mast cells. We compared WT and integrin αlIb-deficient BMMCs as well as integrin αlIb-deficient BMMCs transduced with integrin αIIb(WT) or non-functional αlIb(D163A) mutant and found that enhancement of proliferation, degranulation, cytokine production, and migration of BMMCs through interaction with fibrinogen (FB) depended on integrin αIIbβ3. In addition, elevated surface expression of integrin αVβ3 failed to compensate for loss of FB-associated functions in integrin αIIb-deficient BMMCs while enhancing adhesion to vitronectin or von Willebrand factor. Importantly, integrin αlIb deficiency strongly suppressed chronic inflammation with the remarkable increase of mast cells induced by continuous intraperitoneal administration of FB, although it did not affect acute allergic responses or mast cell numbers in tissues in steady states. Interestingly, soluble FB promoted cytokine production of BMMCs in response to Staphylococcus aureus with FB-binding capacity, through integrin αIIbβ3-dependent recognition of this pathogen. Collectively, integrin αIIbβ3 in mast cells plays an important part in FB-associated, chronic inflammation and innate immune responses. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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