Initial properdin binding contributes to alternative pathway activation at the surface of viable and necrotic cells.

Autor: van Essen MF; Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands., Schlagwein N; Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands., van den Hoven EMP; Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands., van Gijlswijk-Janssen DJ; Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands., Lubbers R; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands., van den Bos RM; Faculty of Science, Department of Chemistry, Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands., van den Born J; Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands., Ruben JM; Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands., Trouw LA; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands., van Kooten C; Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2022 Apr; Vol. 52 (4), pp. 597-608. Date of Electronic Publication: 2022 Feb 17.
DOI: 10.1002/eji.202149259
Abstrakt: Properdin, the only known positive regulator of the complement system, stabilizes the C3 convertase, thereby increasing its half-life. In contrast to most other complement factors, properdin is mainly produced extrahepatically by myeloid cells. Recent data suggest a role for properdin as a pattern recognition molecule. Here, we confirmed previous findings of properdin binding to different necrotic cells including Jurkat T cells. Binding can occur independent of C3, as demonstrated by HAP-1 C3 KO cells, excluding a role for endogenous C3. In view of the cellular source of properdin, interaction with myeloid cells was examined. Properdin bound to the surface of viable monocyte-derived pro- and anti-inflammatory macrophages, but not to DCs. Binding was demonstrated for purified properdin as well as fractionated P2, P3, and P4 properdin oligomers. Binding contributed to local complement activation as determined by C3 and C5b-9 deposition on the cell surfaces and seems a prerequisite for alternative pathway activation. Interaction of properdin with cell surfaces could be inhibited with the tick protein Salp20 and by different polysaccharides, depending on sulfation and chain length. These data identify properdin as a factor interacting with different cell surfaces, being either dead or alive, contributing to the local stimulation of complement activation.
(© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: