Complement lectin pathway components MBL and MASP-1 promote haemostasis upon vessel injury in a microvascular bleeding model.

Golomingi, Murielle; Kohler, Jessie; Jenny, Lorenz; Hardy, Elaissa T; Dobó, József; Gál, Péter; Pál, Gábor; Kiss, Bence; Lam, Wilbur A; Schroeder, Verena (2022). Complement lectin pathway components MBL and MASP-1 promote haemostasis upon vessel injury in a microvascular bleeding model. Frontiers in immunology, 13, p. 948190. Frontiers Research Foundation 10.3389/fimmu.2022.948190

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Background

Complement lectin pathway components, in particular mannan-binding 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 well-defined 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.

Conclusion

We show in a microvascular human bleeding model that MBL and MASP-1 have important roles in the haemostatic response triggered by mechanical vessel injury: MBL recognises the injury site, while MASP-1 increases fibrin formation, platelet activation and shortens bleeding time. While the complement lectin pathway may be harmful in the context of pathological thrombosis, it appears to be beneficial during the physiological coagulation response by supporting the crucial haemostatic system.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Forschungsgruppe Experimentelle Hämostase

UniBE Contributor:

Jenny, Lorenz and Schröder, Verena

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Pubmed Import

Date Deposited:

30 Aug 2022 14:31

Last Modified:

04 Sep 2022 02:16

Publisher DOI:

10.3389/fimmu.2022.948190

PubMed ID:

36032172

Uncontrolled Keywords:

MBL-associated serine protease-1 (MASP-1) complement system haemostasis mannan-binding lectin (MBL) microfluidics

BORIS DOI:

10.48350/172490

URI:

https://boris.unibe.ch/id/eprint/172490

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