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

• Published in: Biochemical and biophysical research communications 2004-08, Vol.321 (2), p.329-336
• Main Authors: Lin, Naisong, Liu, Shuxun, Li, Nan, Wu, Pingping, An, Huazhang, Yu, Yizhi, Wan, Tao, Cao, Xuetao
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Cell Line; Chromosomes, Human, Pair 12 - genetics; Cloning, Molecular; Complement activation; Complement C1r - chemistry; Complement C1r - genetics; Complement C1r - metabolism; Complement subcomponent C1r; Complement System Proteins - immunology; Cytotoxicity, Immunologic; Dendritic cell; Dendritic Cells - enzymology; Dendritic Cells - metabolism; Gene Expression Regulation; Hemolysis; Humans; Inflammation; Molecular Sequence Data; Monocyte; Monocytes - enzymology; Monocytes - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Alignment; Serine Endopeptidases - chemistry; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Serine protease; Trypsin Inhibitors - chemistry; Trypsin Inhibitors - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.06.127

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-α, 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 C1r-like protein might facilitate future investigation of the regulatory mechanism of CLSPa in complement pathways during inflammation.