Increased expression of TRAIL receptor 3 on eosinophils in churg-strauss syndrome

金沢大学医学部附属病院血液浄化療法部Objective. Prolonged survival of eosinophils plays au important role in the pathogenesis of Churg-Strauss syndrome (CSS); however, its detailed molecular mechanism is still unclear. TRAIL and its receptors are expressed on a variety of cells, including eosinophils. In this study, we examined the expression of TRAIL receptors on eosinophils from patients with CSS. Methods. TRAIL receptor expression was assessed on eosinophils from healthy volunteers, patients with CSS, patients with asthma, and patients with hypereosinophilia due to parasitic infection. TRAIL-induced apoptosis of eosinophils was compared between the patients with CSS and patients with asthma. RNA interference was used to assess the effects of suppression of TRAIL receptor 3. Results. Expression of TRAIL receptor 3, a decoy receptor that acts as an antiapoptotic receptor, on eosinophils from patients with CSS was significantly higher than that in the other subjects. Moreover, in CSS, serum TRAIL receptor 3 levels showed a significant positive correlation with peripheral eosinophil counts, tissue-infiltrating eosinophils stained positive for this receptor, and peripheral T cells expressed TRAIL on their surface. Compared with asthma patients, eosinophils from CSS patients showed a significantly lower percentage of recombinant TRAIL, less autologous T cell-induced apoptosis, and decreased level of active caspase 3. Suppression of TRAIL receptor 3 through RNA interference significantly increased the recombinant TRAIL-induced apoptosis of eosinophils from CSS patients. Conclusion. Increased expression of TRAIL receptor 3 on eosinophils from patients with CSS was observed. These alterations in TRAIL receptor 3 expression might be involved in the molecular pathogenesis of CSS eosinophilia. © 2007, American College of Rheumatology

Mouse Heparin Binding Protein-44 (HBP-44) Associates with Brushin, a High-Molecular-Weight Glycoprotein Antigen Common to the Kidney and Teratocarcinomas

Heparin binding protein-44 (HBP-44) is a heparin binding protein of 44 kDa, found by cDNA cloning using antibodies against teratocarcinoma glycoproteins [Furukawa, T. et al. (1990) J. Biochem. 108, 297-302]. The N-terminal sequence analysis reported in this publication establishes the structure of its mature form. Immunohistochemical staining revealed that HBP-44 was located in the tubular brush border of the kidney. HBP-44 formed a complex with brushin, a high molecular weight (460 kDa) glycoprotein antigen common to the kidney and teratocarcinoma, but not with OR8 antigen, another antigen (350 kDa) of the same category. Brushin was shown to be the mouse counterpart of rat Heymann nephritis antigen, called gp330. The association between HBP-44 and brushin was revealed not only by co-precipitation upon indirect immunoprecipitation, but also by ligand blotting with HBP-44-maltose binding protein fusion protein. Calcium ion stabilized the association. Disulfide bonds in brushin seemed to be necessary for the complex formation, since reductive cleavage of the bonds resulted in failure of the protein to associate with HBP-44 in a ligand blotting experiment. Association of HBP-44 with brushin occurred both in teratocarcinoma cells, in which these molecules are mainly located in extraembryonic endoderm cells, and in the kidney, suggesting that the complex has an unknown common function in the renal tubular brush border and the extraembryonic endoderm

Mouse Heparin Binding Protein-44 (HBP-44) Associates with Brushin, a High-Molecular-Weight Glycoprotein Antigen Common to the Kidney and Teratocarcinomas

Heparin binding protein-44 (HBP-44) is a heparin binding protein of 44 kDa, found by cDNA cloning using antibodies against teratocarcinoma glycoproteins [Furukawa, T. et al. (1990) J. Biochem. 108, 297-302]. The N-terminal sequence analysis reported in this publication establishes the structure of its mature form. Immunohistochemical staining revealed that HBP-44 was located in the tubular brush border of the kidney. HBP-44 formed a complex with brushin, a high molecular weight (460 kDa) glycoprotein antigen common to the kidney and teratocarcinoma, but not with OR8 antigen, another antigen (350 kDa) of the same category. Brushin was shown to be the mouse counterpart of rat Heymann nephritis antigen, called gp330. The association between HBP-44 and brushin was revealed not only by co-precipitation upon indirect immunoprecipitation, but also by ligand blotting with HBP-44-maltose binding protein fusion protein. Calcium ion stabilized the association. Disulfide bonds in brushin seemed to be necessary for the complex formation, since reductive cleavage of the bonds resulted in failure of the protein to associate with HBP-44 in a ligand blotting experiment. Association of HBP-44 with brushin occurred both in teratocarcinoma cells, in which these molecules are mainly located in extraembryonic endoderm cells, and in the kidney, suggesting that the complex has an unknown common function in the renal tubular brush border and the extraembryonic endoderm