|Budget Amount *help
¥6,600,000 (Direct Cost : ¥6,600,000)
Fiscal Year 1994 : ¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥4,500,000 (Direct Cost : ¥4,500,000)
Epidermal keratinocytes are connected to each other with desmosomes and to basement membrane with hemidesmosomes so as to form a sheet structure. Hemidesmosomes connsist of 180-KD bullous pemphigoid antigen (BPA), 230-KD BPA and integrins. The purposes of this project are to clarity the regulatory mechanisms of assembly and disassembly of hemidesmosomal molecules and to elucidate the pathomechanisms of blistering and diskeratosis on the basis of regulatory disturbance of cell-jucntions. In 1993, effects of bullous pemphigoid antibody on the morphological mode of assembly and disassembly of hemidesmomal molecules by using anti-180-KD BPA,230-KD BPA and alpha6, beta4 integrins. It was shown that 180-KD BPA is pooled on the lateral plasma membrane without being connected to keratin filaments and the antibody binds to the antigen and the resultant immuncomplexes are internalized, so that molecular assembly of hemidesmosomes is in-hibited (J Dermatol 21 : 838,1994, Dermatology 189, suupl 1 : 46,1994). In addition, we revealed for the first time that phosphorylation of 180-KD BPA,but not of 230-KD BPA,can be induced by phorbol ester (TPA) to increase its molecular weight by 1 KD (Electron Microscopy in Dermatology : Bacic and Clinical Research pp111,1994, Elsevier Science).
In 1994, the mode of signal transduction activated by the antibody-binding to the cell surface antigens of 180-KD BPA and 130-KD pemphigu s vulgar is antigen (PVA) was studied. The binding of pemphigus antibody to its antigen increased transiently the content of IP_3, and Ca^<++> by activating phospholipase C.However, this response was not exerted by the binding of bullous pemphigoid antibody to its antigen on the cell surface. These suggest that the two transmembrane junctional molecules play different roles in signal transduction and intrinsic differences in bristering mechanisms exist between pemhigus and bullous pemphigoid (J Invest Dermatol 104 : 33,1995).