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Tomoaki Nakagawa

Publications and source records attributed to Tomoaki Nakagawa.

8 recordsLinked to original sources
PubMed2005

Mannan-binding protein blocks the activation of metalloproteases meprin alpha and beta.

Mannan-binding protein (MBP) is a C-type serum lectin that is known to be a host defense factor involved in innate immunity, and recognizes mannose, fucose, and N-acetylglucosamine residues. Although some exogenous MBP ligands have been reported, little is known about its endogenous ligands. In the present study, we found that endogenous MBP ligands are highly expressed in the brush border epithelial cells of kidney-proximal tubules by immunohistochemistry, and both meprin alpha and beta (meprins), as novel endogenous MBP ligands, have been identified through affinity chromatography and mass spectrometry. Meprins are membrane-bound and secreted zinc metalloproteases extensively glycosylated and highly expressed in kidney and small intestinal epithelial cells, leukocytes, and certain cancer cells. Meprins are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. Deglycosylation experiments indicated that the MBP ligands on meprins are high mannose- or complex-type N-glycans. The interaction of MBP with meprins resulted in significant decreases in the proteolytic activity and matrix-degrading ability of meprins. Our results suggest that core N-linked oligosaccharides on meprins are associated with the optimal enzymatic activity and that MBP is an important regulator for modulation of the localized meprin proteolytic activity via N-glycan binding. Because meprins are known to be some of the major matrix-degrading metalloproteases in the kidney and intestine, MBP, which functions as a natural and effective inhibitor of meprins, may contribute, as a potential therapeutic target, to tumor progression by facilitating the migration, intravasation, and metastasis of carcinoma cells, and to acute renal failure and inflammatory bowel diseases.

Amino Acid Sequence↗
PubMed2004

Superoxide production from human polymorphonuclear leukocytes by human mannan-binding protein (MBP).

Mannan-binding protein (MBP) is a Ca(2+)-dependent mammalian lectin that plays an important role in innate immunity. In this study, we found that ligand-bound MBP stimulates polymorphonuclear leukocytes (PMN) to induce cell aggregation and superoxide production. The biological response of PMN to ligand-bound MBP was dose- and time-dependent. The PMN aggregation and superoxide production induced by ligand-bound MBP was blocked completely by pertussis toxin, and partially blocked by a platelet activation factor receptor antagonist, TCV-309. These findings suggest that the ligand-bound MBP stimulates PMN through a putative MBP receptor(s) on PMN.

Calcium↗
PubMed2003

Participation of a fusogenic protein, glyceraldehyde-3-phosphate dehydrogenase, in nuclear membrane assembly.

We found an autoimmune serum, K199, that strongly suppresses nuclear membrane assembly in a cell-free system involving a Xenopus egg extract. Four different antibodies that suppress nuclear assembly were affinity-purified from the serum using Xenopus egg cytosol proteins. Three proteins recognized by these antibodies were identified by partial amino acid sequencing to be glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fructose-1,6-bisphosphate aldolase, and the regulator of chromatin condensation 1. GAPDH is known to be a fusogenic protein. To verify the participation of GAPDH in nuclear membrane fusion, authentic antibodies against human and rat GAPDH were applied, and strong suppression of nuclear assembly at the nuclear membrane fusion step was observed. The nuclear assembly activity suppressed by antibodies was recovered on the addition of purified chicken GAPDH. A peptide with the sequence of amino acid residues 70-94 of GAPDH, which inhibits GAPDH-induced phospholipid vesicle fusion, inhibited nuclear assembly at the nuclear membrane fusion step. We propose that GAPDH plays a crucial role in the membrane fusion step in nuclear assembly in a Xenopus egg extract cell-free system.

Amino Acid Sequence↗
PubMed2002

L-MBP is expressed in epithelial cells of mouse small intestine.

The mannan-binding proteins (L-MBP and S-MBP, also denoted MBL-C and MBL-A), mainly produced in liver and existing in liver and serum, play important roles in the innate immunity against a variety of pathogens. Total RNA from mouse tissues were screened for MBP mRNA by RT-PCR. In addition to liver, S-MBP mRNA was detected in lung, kidney, and testis, and L-MBP mRNA was detected in kidney, thymus, and small intestine. Quantitative RT-PCR revealed that the small intestine is a predominant site of extrahepatic expression of L-MBP. Western blotting with polyclonal Abs against rat L-MBP demonstrated this protein in Triton X-100 extracts of the small intestine obtained from mice that had undergone systemic perfusion. Immunohistochemical staining with an mAb against mouse L-MBP and in situ hybridization revealed that L-MBP is selectively expressed in some villous epithelial cells of the small intestine. These findings suggest that L-MBP plays a role in mucosal innate immunity.

Animals↗
PubMedDate not supplied

Role of mannan-binding protein, MBP, in innate immunity.

Mannan-binding protein (MBP) is a C-type lectin, which binds to carbohydrates on the surface of some microorganisms and kills them through the activation of complement. This complement activation pathway is called the lectin pathway. MBP also kills mammalian cells that express MBP ligands on their surfaces via the lectin pathway. Recently, we found anti-tumor activity of MBP in vivo using tumor cells transplanted into nude mice. We propose to call this anti-tumor effect mannan-binding protein-dependent cell-mediated cytotoxicity (MDCC), because it does not require complement activation, and the involvement of some immune cells was assumed. Very recently, MBP was demonstrated to be selectively expressed in epithelial cells of the small intestine. This finding may suggest that MBP plays an important role in the small intestine as a host defense factor.

Animals↗