Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly

Research output: Contribution to journalArticle

202 Scopus citations

Abstract

Complement promotes the rapid recognition and elimination of pathogens, infected cells, and immune complexes. The biochemical basis for its target specificity is incompletely understood. In this report, we demonstrate that properdin can directly bind to microbial targets and provide a platform for the in situ assembly and function of the alternative pathway C3 convertases. This mechanism differs from the standard model wherein nascent C3b generated in the fluid phase attaches nonspecifically to its targets. Properdin-directed complement activation occurred on yeast cell walls (zymosan) and Neisseria gonorrhoeae. Properdin did not bind wild-type Escherichia coli, but it readily bound E. coli LPS mutants, and the properdin-binding capacity of each strain correlated with its respective serum-dependent AP activation rate. Moreover, properdin:single-chain Ab constructs were used to direct serum-dependent complement activation to novel targets. We conclude properdin participates in two distinct complement activation pathways: one that occurs by the standard model and one that proceeds by the properdin-directed model. The properdin-directed model is consistent with a proposal made by Pillemer and his colleagues >50 years ago.

Original languageEnglish
Pages (from-to)2600-2608
Number of pages9
JournalJournal of Immunology
Volume179
Issue number4
DOIs
StatePublished - Aug 15 2007

Fingerprint Dive into the research topics of 'Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly'. Together they form a unique fingerprint.

  • Cite this