Abstract
Properdin, the only positive regulatory protein of the complement system, acts as both a stabilizer of the alternative pathway (AP) convertases and as a selective pattern recognition molecule of certain microorganisms and host cells (i.e., apoptotic/necrotic cells) by serving as a platform for de novo C3b,Bb assembly. Properdin, a highly positively charged protein, normally exists as cyclic dimers (P2), trimers (P3), and tetramers (P4) of head-to-tail associations of monomeric 53 kDa subunits. While most complement proteins are produced mainly in the liver, properdin is synthesized primarily by various cell types, including neutrophils, monocytes, primary T cells, and shear-stressed endothelial cells resulting in properdin serum levels of 4–25 μg/ml. Multiple inflammatory agonists stimulate the release of properdin from stimulated leukocytes into the cellular microenvironment. Concentrated, focused increases in properdin levels may lead to stabilization and initiation of AP convertases, thus greatly amplifying the complement response to a local stimulus. This review highlights current knowledge related to these properties and discusses the implications of properdin production in a pro-inflammatory microenvironment.
Highlights
THE COMPLEMENT SYSTEM ALTERNATIVE PATHWAY The complement system efficiently defends the host from pathogenic microorganisms, facilitates removal of immune complexes, and represents an important link between the innate and adaptive immune systems
The alternative pathway (AP) plays a fundamental role in the amplification of all three pathways because C3b molecules generated by the classical and lectin pathways contribute to generating AP C3 convertases (Harboe and Mollnes, 2008; Gulati et al, 2012)
Unlike the classical and lectin pathways that rely on specific recognition molecules (C1q and mannan binding lectin/ficolins, respectively) for initiation, the AP activates on any surface that lacks the ability to regulate complement
Summary
THE COMPLEMENT SYSTEM ALTERNATIVE PATHWAY The complement system efficiently defends the host from pathogenic microorganisms, facilitates removal of immune complexes, and represents an important link between the innate and adaptive immune systems. The only positive regulatory protein of the complement system, and the focus of this review, extends the half-life of the nascent C3b,Bb convertase (5–10-fold) by forming the complex C3b,Bb,P (Fearon and Austen, 1975; Schreiber et al, 1975), leading to accelerated and efficient amplification of C3b deposition on surfaces (Muller-Eberhard and Gotze, 1972; Pangburn, 1998; Rother, 1998).
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