| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Glycosylation signals control critical lymphocyte processes, including lymphocyte homing, thymocyte selection, and immune response amplitude. Regulated glycosylation of specific acceptor substrates can affect immune functions by creating or masking ligands for endogenous lectins. This research aimed at the regulation of immune responses through glycosylation signals in immunobiology and application, and the following results were clarified.
1. Colorectal tumor-associated Le^a/Le^b glycans are important ligands for DC-SIGN on carcinoma cell lines and primary cancer colon epithelia, and glycosylation-dependent interactions between DC-SIGN and colorectal tumor-associated Le glycans strongly enhanced LPS-induced anti-inflammatory cytokines IL-6 and IL-10 secretion by MoDCs and the LPS-induced functional maturation of MoDCs was strikingly inhibited by supernatants of cocultures with the carcinoma cells. These results suggest that DC-SIGN, upon binding of colorectal tumor-associated Le^a/Le^b
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glycans, may interfere with TLR-mediated signals.
2. Macrophage asialoglycoprotein-binding protein(M-ASGP-BP) is a Gal/GalNAc-specific lectin, which functions as an endocytosis receptor. We found that LPS is able to down-regulate the mRNA expression of M-ASGP-BP in a time-dependent manner using thioglycolate-elicited rat and mouse peritoneal macrophages, and the mRNA expression of M-ASGP-BP is down-regulated by the LPS-mediated TLR4 pathway involving NF-kB activation.
3. CD26 was identified as a novel DC-SIGN ligand on T lymphocytes, and ADA and CD45 were also detected in the co-immunoprecipitates both with anti-CD26 and anti-DC-SIGN antibodies, suggesting that the cluster of DC-SIGN and CD26-ADA-CD45 complex may play an important role in the formation of the immune synapse and the costimulatory signaling.
4. A novel phosphomannan-binding lectin (PMBL) was isolated and characterized from both newborn and adult porcine serum. Porcine PMBL functionally activated the complement system through the lectin pathway triggered by binding with both phosphomannan and mannan, which, unlike MBP, was effectively inhibited by mannose-6-phosphate-or galatose-containing oligosaccharides. Less
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