A

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

European Journal of Immunology, vol. 52, pp. 597–608

Abstract

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.

Authors 10

  1. Leiden University Medical Center

    Affiliation as printed

    Division of Nephrology and Transplant Medicine Department of Medicine Leiden University Medical Center Leiden The Netherlands

    Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

  2. Leiden University Medical Center

    Affiliation as printed

    Division of Nephrology and Transplant Medicine Department of Medicine Leiden University Medical Center Leiden The Netherlands

    Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

  3. Leiden University Medical Center

    Affiliation as printed

    Division of Nephrology and Transplant Medicine Department of Medicine Leiden University Medical Center Leiden The Netherlands

    Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

  4. Leiden University Medical Center

    Affiliation as printed

    Division of Nephrology and Transplant Medicine Department of Medicine Leiden University Medical Center Leiden The Netherlands

    Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

  5. Leiden University Medical Center

    Affiliation as printed

    Department of Rheumatology Leiden University Medical Center Leiden The Netherlands

    Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

  6. Utrecht University

    Affiliation as printed

    Faculty of Science Department of Chemistry Crystal and Structural Chemistry Bijvoet Center for Biomolecular Research Utrecht University Utrecht The Netherlands

    Faculty of Science, Department of Chemistry, Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands

  7. University Medical Center Groningen

    Affiliation as printed

    Department of Nephrology University Medical Center Groningen Groningen The Netherlands

    Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands

  8. Leiden University Medical Center · Cancer Center Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

    Affiliation as printed

    Division of Nephrology and Transplant Medicine Department of Medicine Leiden University Medical Center Leiden The Netherlands

    Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

    Present address: Amsterdam UMC, location VUmc, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands

  9. Leiden University Medical Center

    Affiliation as printed

    Department of Immunology Leiden University Medical Center Leiden The Netherlands

    Department of Rheumatology Leiden University Medical Center Leiden The Netherlands

    Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands

    Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

  10. Leiden University Medical Center

    Affiliation as printed

    Division of Nephrology and Transplant Medicine Department of Medicine Leiden University Medical Center Leiden The Netherlands

    Division of Nephrology and Transplant Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

Cited by 8 stored of 8

8 results

No patents citing this paper on Lens.org (checked 2026-10-11).

References 43