A novel human dendritic cell-derived C1r-like serine protease analog inhibits complement-mediated cytotoxicity.
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.
Lin
Naisong
N
Institute of Immunology, Zhejiang University, 353 Yan'an Road, Hangzhou 310031, PR China.
Liu
Shuxun
S
Li
Nan
N
Wu
Pingping
P
An
Huazhang
H
Yu
Yizhi
Y
Wan
Tao
T
Cao
Xuetao
X
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003001:Cloning, Molecular; D015923:Complement C1r / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000201:enzymology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006461:Hemolysis; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000378:metabolism
D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D003165:Complement System Proteins; D012697:Serine Endopeptidases; D015923:Complement C1r