Mannose-binding lectin-associated serine protease-1 cleaves plasminogen and plasma fibronectin: prefers plasminogen over known fibrinogen substrate

Abstract

Mannose-binding lectin-associated serine protease-1 (MASP-1) is known to interact with complement and coagulation pathways. Recently it was reported that MASP-1 interacts with the fibrinolytic system but details remain unclear. The objective of the study is to find MASP-1 substrates that participate in the fibrinolytic system. Commercially available fibrinogen might contain some impurities. Fibrinogen was treated with MASP-1 followed by analysis on SDS–PAGE and the obtained cleaved fragments were identified by matrix-assisted laser desorption/ionization-time of flight/time of flight. Functional analysis of identified substrate was confirmed by fluorogenic and turbidimetric assay. Statistical analysis was done by using the Student t test. This study reports that plasminogen and plasma fibronectin are two hitherto unknown substrates of MASP-1. Conversion of plasminogen to plasmin like molecule by MASP-1 was confirmed by cleavage of plasmin specific substrate and digestion of fibrin clot. The role of MASP-1 in clot dissolution was confirmed by turbidity assay. Our study shows that MASP-1 selects plasminogen over fibrinogen to be a preferable substrate. MASP-1 promotes the fibrinolytic activity by the generation of plasmin like molecule from plasminogen and further destabilizes the clot by digestion of plasma fibronectin.

The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency

“…S8B ). Interestingly, some of these proteins have been related to immune functions, e.g., SERPINA 3 [ 24 ], MASP1 [ 25 ] and AI182371 (GO annotation), or to pathophysiological conditions of the CNS, e.g., SERPINA 3 [ 26 ] and PZP [ 27 , 28 ]. The levels of the other 11 proteins were also modified after β-RA and VA treatment compared to vehicle treatment, although they were not altered in Coq9 R239X mice compared to wild-type mice ( Fig.…”

SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE

“…However, plasma kallikrein has been recognized as a pro-convertase, with anaphylatoxin production ( 6 ). In addition to anaphylatoxin generation, complement proteases promote plasminogen activation ( 7 ), with plasmin production that in turn triggers KKS. This latter proteolytic system directly cleaves circulating high molecular weight kininogen, subsequently generating BK production.…”