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A novel human dendritic cell-derived C1r-like serine protease analog inhibits complement-mediated cytotoxicity.

Authors
  • Lin, Naisong
  • Liu, Shuxun
  • Li, Nan
  • Wu, Pingping
  • An, Huazhang
  • Yu, Yizhi
  • Wan, Tao
  • Cao, Xuetao
Type
Published Article
Journal
Biochemical and biophysical research communications
Publication Date
Aug 20, 2004
Volume
321
Issue
2
Pages
329–336
Identifiers
PMID: 15358180
Source
Medline
License
Unknown

Abstract

Trypsin-like serine proteases are involved in diverse biological processes such as complement activation, tissue remodeling, cellular migration, tumor invasion, and metastasis. Here we report a novel human C1r-like serine protease analog, CLSPa, derived from dendritic cells (DC). The 487-residue CLSPa protein contains a CUB domain and a serine protease domain, possessing characteristic catalytic triad but lacking typical activation/cleavage sequence. It shares great homology with complement C1r/C1s and mannose-associated serine proteases. CLSPa mRNA is widely expressed, especially abundant in placenta, liver, kidney, pancreas, and myeloid cells, which are a major resources of serine proteases. Upon stimulation by agonistic anti-CD40 Ab, TNF-alpha, or LPS, CLSPa mRNA expression was significantly up-regulated in monocytic cells and monocyte-derived immature DC. When overexpressed in 293T cells, CLSPa protein was synthesized into the culture supernatants as a secretory protein, which had an inhibitory effect on complement-mediated cytotoxicity to antibody-sensitized erythrocytes. However, CLSPa itself possesses little protease activity, but it plays an inhibitory role in other active protease catalytic processes. The identification of human CLSPa as a novel Clr-like protein might facilitate future investigation of the regulatory mechanism of CLSPa in complement pathways during inflammation.

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