Proteinase 3 Interferes With C1q-Mediated Clearance of Apoptotic Cells

Frontiers in Immunology
Pascale Tacnet-DelormeVéronique Witko-Sarsat

Abstract

Proteinase 3 (PR3) is the autoantigen in granulomatosis with polyangiitis, an autoimmune necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Moreover, PR3 is a serine protease whose membrane expression can potentiate inflammatory diseases such as ANCA-associated vasculitis and rheumatoid arthritis. During apoptosis, PR3 is co-externalized with phosphatidylserine (PS) and is known to modulate the clearance of apoptotic cells through a calreticulin (CRT)-dependent mechanism. The complement protein C1q is one mediator of efferocytosis, the clearance of altered self-cells, particularly apoptotic cells. Since PR3 and C1q are both involved in the clearance of apoptotic cells and immune response modulation and share certain common ligands (i.e., CRT and PS), we examined their possible interaction. We demonstrated that C1q binding was increased on apoptotic rat basophilic leukemia (RBL) cells that expressed PR3, and we demonstrated the direct interaction between purified C1q and PR3 molecules as shown by surface plasmon resonance. To better understand the functional consequence of this partnership, we tested C1q-dependent phagocytosis of the RBL cell line expressing PR3 and showed that PR3 impaired C1...Continue Reading

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Citations

Jul 25, 2018·European Journal of Clinical Investigation·Nathalie ThieblemontAmiram Ariel
Jul 7, 2020·Frontiers in Pharmacology·Hiba YaseenAmiram Ariel
Nov 22, 2018·Current Opinion in Rheumatology·Maria A C Wester TrejoIngeborg M Bajema
Jan 12, 2021·Vascular·Dobroslav KyurkchievEkaterina Ivanova-Todorova
Oct 28, 2021·Immunology·Apurwa Singhal, Sachin Kumar

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Methods Mentioned

BETA
density-gradient centrifugation
PMA
flow cytometry
FCS
chip
confocal microscopy

Software Mentioned

BIAevaluation
MACSQuantify

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