Mannan-binding protein blocks the activation of metalloproteases meprin α and β

Makoto Hirano, Bruce Yong Ma, Nana Kawasaki, Kazumichi Okimura, Makoto Baba, Tomoaki Nakagawa, Keiko Miwa, Nobuko Kawasaki, Shogo Oka, Toshisuke Kawasaki

研究成果: ジャーナルへの寄稿学術論文査読

39 被引用数 (Scopus)

抄録

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 α and β (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.

本文言語英語
ページ(範囲)3177-3185
ページ数9
ジャーナルJournal of Immunology
175
5
DOI
出版ステータス出版済み - 01-09-2005
外部発表はい

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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