Activation of the alternative complement pathway: Recognition of surface structures on activators by bound C3b

M. K. Pangburn, D. C. Morrison, R. D. Schreiber, H. J. Muller-Eberhard

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

A soluble lipopolysaccharide (LPS) was isolated from Escherichia coli strain 04 and after mild alkaline hydrolysis was incorporated into the membrane of sheep erythrocytes (E(s)), which do not themselves activate the alternative complement pathway. The modified cells were found to activate the pathway. The ability to create an activating surface by incorporation of a foreign molecule allowed an examination of the mechanism of activator recognition by surface-bound C3b. When C3b was first deposited on the surface of E(s) and varying amounts of LPS subsequently were incorporated into the membrane, a dose-dependent decrease in binding of the control protein β1H to C3b was observed. The maximum effect required approximately 120,000 monomer LPS molecules per cell carrying 20,000 C3b molecules. No decrease in Factor B binding to C3b occurred, demonstrating the specificity of the effect. Concomitantly, the functional half-life of the cell bound C3b exposed to the serum control proteins was increased 3-fold. Sialic acid appears to play no role in this mechanism, since the LPS did not contain this carbohydrate and the sialic acid content of E(s) was not altered by LPS incorporation. The results indicate that cell bound C3b possesses a recognition site that is distinct from the metastable binding site of C3b and that allows discrimination between nonactivating and activating surfaces. Surface structures (β1H antagonists) that interact with the discriminatory site on C3b restrict alternative pathway control and thereby activate the pathway.

Original languageEnglish
Pages (from-to)977-982
Number of pages6
JournalJournal of Immunology
Volume124
Issue number2
StatePublished - Jan 1 1980
Externally publishedYes

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