Identifying the functional part of heparin-binding protein (HBP) as a monocyte stimulator and the novel role of monocytes as HBP producers:

Innate Immunity

MortenSchou¹ 

关键词: heparin-binding protein;    monocytes;    HBP;    HBP peptide;   

DOI  :  10.1177/1753425909354763

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

Heparin-binding protein (HBP), an evolutionary ancient and biologically highly important molecule in inflammation, is an inactive serine protease due to mutations in the catalytic triad. The histidine (position 41) in the conserved sequence TAAHC is mutated to serine and this sequence (TAASC) plays a crucial role when HBP binds to monocytes. We synthesized a 20—44 HBP peptide, cyclicized by a sulphur bridge, which encompasses this amino acid and functions as full-length HBP. Using a human monocyte cell line, we have shown that lipopolysaccharide (LPS)-triggered secretion of IL-6 is enhanced up to 10-fold when full-length HBP or the peptide are present in low-to-moderate concentrations. A monoclonal antibody neutralizing HBP also neutralizes the peptide, indicating that the ligand for the HBP receptor is located near serine in position 41 on the HBP surface. A ‘back mutated’ 20—44 peptide (serine→histidine) has some, but not significant, stimulatory effect on monocytes. Normally, HBP production and release...

【 授权许可】

CC BY