Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Collagen VI Contains Multiple Host Defense Peptides with Potent In Vivo Activity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Multiple Homozygous Variants in the STING-Encoding TMEM173 Gene in HIV Long-Term Nonprogressors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Cyclodextrin Reduces Cholesterol Crystal-Induced Inflammation by Modulating Complement Activation

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Plasma levels of mannose-binding lectin and future risk of venous thromboembolism

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Immune regulation by fibroblasts in tissue injury depends on uPARAP-mediated uptake of collectins

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Complement Nomenclature-Deconvoluted

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Soluble defense collagens including the collectins play important roles in innate immunity. Recently, a new member of the collectin family named collectin-12 (CL-12 or CL-P1) has been identified. CL-12 is highly expressed in umbilical cord vascular endothelial cells as a transmembrane receptor and may recognize certain bacteria and fungi, leading to opsonophagocytosis. However, based on its structural and functional similarities with soluble collectins, we hypothesized the existence of a fluid-phase analog of CL-12 released from cells, which may function as a soluble pattern-recognition molecule. Using recombinant CL-12 full length or CL-12 extracellular domain, we determined the occurrence of soluble CL-12 shed from in vitro cultured cells. Western blot showed that soluble recombinant CL-12 migrated with a band corresponding to ∼120 kDa under reducing conditions, whereas under nonreducing conditions it presented multimeric assembly forms. Immunoprecipitation and Western blot analysis of human umbilical cord plasma enabled identification of a natural soluble form of CL-12 having an electrophoretic mobility pattern close to that of shed soluble recombinant CL-12. Soluble CL-12 could recognize Aspergillus fumigatus partially through the carbohydrate-recognition domain in a Ca(2+)-independent manner. This led to activation of the alternative pathway of complement exclusively via association with properdin on A. fumigatus as validated by detection of C3b deposition and formation of the terminal complement complex. These results demonstrate the existence of CL-12 in a soluble form and indicate a novel mechanism by which the alternative pathway of complement may be triggered directly by a soluble pattern-recognition molecule.

OriginalsprogEngelsk
TidsskriftJournal of immunology (Baltimore, Md. : 1950)
Vol/bind195
Udgave nummer7
Sider (fra-til)3365-73
Antal sider9
ISSN0022-1767
DOI
StatusUdgivet - 1 okt. 2015

ID: 45692488