Mannose‐binding lectin concentrations correlate with enhanced whole blood aggregation and thrombin‐like activity in humans

Abstract

Mannose‐binding lectin (MBL) and its associated serine proteases (MASPs) are part of the lectin pathway of complement system activation. Recently, the MBL‐complex was shown to have thrombin‐like activity in cellular and murine models, suggesting the complement and coagulation systems interact. The purpose of this study was to determine if the MBL‐complex displays thrombin‐like activity in human whole blood aggregation. Sera from low, normal, and high MBL‐expressing donors were collected and analyzed for thrombin‐like activity using the chromogenic thrombin substrate, S2238. In addition, blood was collected from 14 healthy human volunteers and whole blood aggregation (Chronolog) was assessed. Thrombin substrate cleavage correlated with increasing MBL levels (p < 0.001), and could be inhibited by GlcNAc, a competitive MBL inhibitor, verifying that the observed cleavage was MBL‐complex dependent. Whole blood aggregation was enhanced in donors with normal MBL levels (501 – 2000 ng/mL) compared to low MBL donors (<500 ng/ml; p < 0.01). However, no significant difference in whole blood aggregation was found between normal and high MBL donors, suggesting a saturation‐type effect. These results indicate that human MBL complex activation in vitro significantly activates the coagulation system in whole blood. Further study is required to determine the role of human MBL in in vivo coagulation.