The emerging roles of mannose‐binding lectin‐associated serine proteases (MASPs) in the lectin pathway of complement and beyond

Immunological Reviews - Tập 274 Số 1 - Trang 98-111 - 2016
József Dobó1, Gábor Pál2, László Cervenak3, Péter Gál1
1Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary
2Department of Biochemistry, Eötvös Loránd University, Budapest, Hungary
33rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary

Tóm tắt

Summary

Mannose‐binding lectin (MBL)‐associated serine proteases (MASPs) are the enzymatic constituents of the lectin pathway of the complement system. They are complexed with large pattern recognition molecules (PRMs) such as MBL, other collectins, and ficolins. The main function of two of the three MASPs has crystallized lately: MASP‐1 autoactivates first, then it activates MASP‐2, and finally both participate in the formation of the C4b2a convertase. In addition to this, both enzymes are involved in several other processes which are subject to intense research nowadays. Notably, MASP‐1, as a promiscuous enzyme, has been implicated in the coagulation cascade, in the kinin generating contact system, and in cellular activation through protease‐activated receptor (PAR) cleavage on endothelial cells. The third protease MASP‐3 has emerged recently as the protease responsible for pro‐factor D activation in resting blood, providing a fundamental link between two complement pathways. At present all three MASPs have at least one well‐defined role and several other possible functions were implicated. Defect or more likely over‐activation of MASPs may culminate into diseases such as ischemia–reperfusion injury (IRI); hence, MASPs are all potential targets of drug development.

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