The complement system is a key part of the innate and adaptive immune system and plays a major role in homeostasis by clearing altered host cells and invading pathogens. Compstatin, a 13-residue peptide, is an effective inhibitor of the activation of complement component C3 with IC50 value of 12 μM and thus blocks a central and crucial step in the complement cascade[1]. In vitro studies of compstatin in human blood indicated that a major pathway of biotransformation was the removal of Ile1, which could be blocked by N-acetylation of the peptide[2]. Subsequent interaction analysis confirmed that compstatin binds NHP C3 (baboon) and human C3 with similar affinity, but it does not bind to mouse or rat C3[3]. Compstatin produced complete inhibition at a total dose of 21 mg/kg when given as a combination of bolus injection and infusion. It completely inhibited in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures[4].
作用机制
The crystal structure reveals that the compstatin-binding site is formed by the macroglobulin (MG) domains 4 and 5[1].
Compstatin/坎普他汀 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CD8+ T cells
20 μg/ml
5-7 days
Does not affect the production of IL-2 and TNF-α
Bone Marrow Transplant. 2014 Jul;49(7):972-6.
CD4+ T cells
20 μg/ml
5-7 days
Inhibits Th1/Th17 polarization and reduces IL-2 and TNF-α production
Bone Marrow Transplant. 2014 Jul;49(7):972-6.
Human neutrophils
250 ng/ml
4 hours
To investigate the effect of proteases released from C5a-activated neutrophils on VE-cadherin degradation. Results showed that proteases released from C5a-activated neutrophils (particularly neutrophil elastase) led to VE-cadherin degradation and intercellular gap formation.
Mol Immunol. 2019 Oct;114:629-642.
Human immortalized gingival keratinocytes (HIGK)
500 ng/ml
24 hours
To investigate the mechanism of C3a-induced IL-6 release in response to bacterial stimulation, results showed that C3a synergistically increased IL-6 release when combined with Pam3Cys or P. gingivalis.
Inhibition of complement activation in human fetal RPE cells assessed as reduction in C5b-9 formation at 50 uM by fluorescence assay in presence of complement-competant human serum
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