Complement lectin pathway components MBL and MASP-1 promote haemostasis upon vessel injury in a microvascular bleeding model
Authors
Murielle Golomingi, Jessie Kohler, Lorenz Jenny, Elaissa T. Hardy, Jozsef Dobo, Peter Ga, Gabor Pa, Bence Kiss, Wilbur A. Lam and Verena Schroeder
Institution
DBMR, University of Bern, Bern, Switzerland
Country
Switzerland
Year
2022
Journal
Frontiers in Immunology
Abstract
Background: Complement lectin pathway components, in particular mannanbinding
lectin (MBL) and MBL-associated serine proteases (MASPs) have been
shown to interact with coagulation factors and contribute to clot formation.
Here we investigated the role of MBL and MASP-1 in the haemostatic response
following mechanical vessel injury in a human microfluidic bleeding model.
Methods: We studied haemostasis in a microvascular bleeding model in the
presence of human endothelial cells and human whole blood under flow
conditions. We monitored incorporation of proteins into the clot with
fluorescently labelled antibodies and studied their effects on clot formation,
platelet activation, and bleeding time with specific inhibitors. Platelet activation
was also studied by flow cytometry.
Results: Upon vessel injury, MBL accumulated at the injury site in a welldefined
wall-like structure. MBL showed partial colocalisation with fibrin, and
strong colocalisation with von Willebrand factor and (activated) platelets. Flow
cytometry ruled out direct binding of MBL to platelets, but confirmed a PAR4-
and thrombin-dependent platelet-activating function of MASP-1. Inhibiting
MBL during haemostasis reduced platelet activation, while inhibiting MASP-1
reduced platelet activation, fibrin deposition and prolonged bleeding time.