Inhibition of CXCL10 release by monomeric C3bi and C4b.

Cellulose acetate (CA) beads are often used for leucocyte apheresis therapy against inflammatory bowel disease. In order to clarify the mechanism of the anti-inflammatory effects of CA, global analysis of the molecules generated in blood by the interaction with CA beads was performed in this study. An activated medium was collected from whole blood that had been preincubated with CA beads, and the effects of the CA-activated medium on leucocyte function were investigated. Fresh blood was stimulated with lipopolysaccharide (LPS) or interferon (IFN)-ß in the presence of the activated medium, and levels of chemokines and cytokines, including CXCL10 (IFN-inducible protein-10), and phosphorylated STAT1 (signal transducer and activator of transcription 1), which is known to be essential for CXCL10 production in leucocytes, were measured. IFN-ß- or LPS-induced CXCL10 production, expression of CXCL10 mRNA and phosphorylation of STAT1 were significantly reduced in the presence of the medium pretreated with CA beads compared with the control without the CA bead treatment. The factors inhibiting CXCL10 production were identified as the C3 and C4 fragments by mass spectrometry. The monomeric C3bi and C4b proteins were abundant in the medium pretreated with CA beads. Furthermore, purified C3bi and C4b were found to inhibit IFN-ß-induced CXCL10 production and STAT1 phosphorylation. Thus, STAT1-mediated CXCL10 production induced by stimulation with LPS or IFN was potently inhibited by monomeric C3bi and C4b generated by the interaction of blood with CA beads. These mechanisms mediated by monomeric C3bi and C4b may be involved in the anti-inflammatory effects of CA.

Stimulation of the regrowth of MPP+-damaged dopaminergic fibers by the treatment of mesencephalic cultures with basigin.

Basigin (Bsg) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily and widely expressed in the central nervous system. To elucidate functional role of Bsg in the central nervous system, the effects of its glutathione-S-transferase (GST) fusion protein on the number and neurite outgrowth of cultured rat mesencephalic dopaminergic neurons were measured. The fusion protein was not able to promote the survival and neurite outgrowth of tyrosine hydroxylase (TH)-positive neurons under serum-free condition. However, the treatment of 1-methyl-4-phenylpyridinium (MPP+)-exposed cultures with the fusion protein resulted in stimulation of the regrowth of damaged TH-positive fibers. Basic fibroblast growth factor (bFGF) also stimulated the regrowth of neurites in damaged neurons. These results indicate that Bsg may play an important role in the regrowth of damaged dopaminergic fibers.

Structure of the mouse basigin gene, a unique member of the immunoglobulin superfamily.

Basigin is a membrane glycoprotein belonging to the immunoglobulin superfamily. The mouse basigin gene was isolated from a genomic DNA library of the BALB/c mouse, and the structure of the gene and its flanking region (11.8 kb) was completely determined. The mouse basigin gene consists of seven exons and six introns spanning 7.5 kb. The distance between the first and second exons is 5.1 kb. The first immunoglobulin-like domain of the basigin molecule is encoded by the second and third exons, and the second immunoglobulin-like domain by the fourth and fifth exons. The fifth exon encodes not only the C proximal portion of the second immunoglobulin-like domain, but also the transmembrane domain and a small portion of the cytoplasmic domain. Thus, the organization of the basigin gene is unique. The 5' upstream sequence of the basigin gene contains no TATA box or CAAT box, but has a CpG-rich island. The BALB/c genomic sequence of all seven exons is consistent with the cDNA sequences of the 129/SV and Swiss mice except several minor substitutions in the 3'-terminal sequence of the 3'-noncoding region. No protein polymorphism has so far been found in basigin of different mouse strains.