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Sci Rep. 2017 Dec 5;7(1):16958. doi: 10.1038/s41598-017-17318-w.

Interaction of Complement Defence Collagens C1q and Mannose-Binding Lectin with BMP-1/Tolloid-like Proteinases.

Author information

1
Univ. Grenoble Alpes, CNRS, CEA, IBS, F-38000, Grenoble, France.
2
Univ. Lyon, Université Claude Bernard Lyon 1, CNRS, Tissue Biology and Therapeutic Engineering Unit, LBTI, UMR 5305, F-69367, Lyon, France.
3
Laboratoire d'Immunologie, Pôle de Biologie, CHU Grenoble Alpes, 38700, La Tronche, France.
4
BNI group, TIMC-IMAG UMR5525 Université Grenoble Alpes, 38706, La Tronche, France.
5
Department of Dermatology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
6
Univ. Lyon, University Claude Bernard Lyon 1, INSA Lyon, CPE, Institute of Molecular and Supramolecular Chemistry and Biochemistry (ICBMS), UMR 5246, F-69622, Villeurbanne, France.
7
Univ. Lyon, Université Claude Bernard Lyon 1, CNRS, Tissue Biology and Therapeutic Engineering Unit, LBTI, UMR 5305, F-69367, Lyon, France. david.hulmes@ibcp.fr.
8
Univ. Grenoble Alpes, CNRS, CEA, IBS, F-38000, Grenoble, France. nicole.thielens@ibs.fr.

Abstract

The defence collagens C1q and mannose-binding lectin (MBL) are immune recognition proteins that associate with the serine proteinases C1r/C1s and MBL-associated serine proteases (MASPs) to trigger activation of complement, a major innate immune system. Bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases (BTPs) are metalloproteinases with major roles in extracellular matrix assembly and growth factor signalling. Despite their different functions, C1r/C1s/MASPs and BTPs share structural similarities, including a specific CUB-EGF-CUB domain arrangement found only in these enzymes that mediates interactions with collagen-like proteins, suggesting a possible functional relationship. Here we investigated the potential interactions between the defence collagens C1q and MBL and the BTPs BMP-1 and mammalian tolloid-like-1 (mTLL-1). C1q and MBL bound to immobilized BMP-1 and mTLL-1 with nanomolar affinities. These interactions involved the collagen-like regions of the defence collagens and were inhibited by pre-incubation of C1q or MBL with their cognate complement proteinases. Soluble BMP-1 and mTLL-1 did not inhibit complement activation and the defence collagens were neither substrates nor inhibitors of BMP-1. Finally, C1q co-localized with BMP-1 in skin biopsies following melanoma excision and from patients with recessive dystrophic epidermolysis bullosa. The observed interactions provide support for a functional link between complement and BTPs during inflammation and tissue repair.

PMID:
29209066
PMCID:
PMC5717261
DOI:
10.1038/s41598-017-17318-w
[Indexed for MEDLINE]
Free PMC Article

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