The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis

TLDR

Apoptotic cells must be cleared rapidly to prevent inflammation, and innate immunity recognizes dying cells through unique surface patterns. We show that properdin binds early apoptotic T cells via surface proteoglycan glycosaminoglycans, triggers complement activation and C3b opsonization for phagocytosis, and also promotes phagocyte uptake independently of complement, with neutrophil‑derived properdin being particularly effective and serum properdin inhibited, suggesting a broader role in apoptosis clearance.

Abstract

Apoptotic cells must be rapidly eliminated to avoid harmful inflammatory and autoimmune reactions. Innate immunity is designed/poised to identify dying cells by their unique surface-associated molecular patterns. Here we demonstrate for the first time, to our knowledge, that the human complement protein properdin binds to early apoptotic T cells and initiates complement activation, leading to C3b opsonization and ingestion by phagocytic cells. Properdin binding was facilitated by the glycosaminoglycan chains of surface proteoglycans. Properdin released by activated neutrophils was particularly effective at recognition of apoptotic T cells, whereas the binding activity of properdin in the serum appeared to be inhibited. “Properdin tagging” of apoptotic T cells also induced their uptake by phagocytes independent of complement activation or other complement proteins. Although our findings were made primarily with apoptotic T cells, they suggest that properdin could play a similar role during apoptosis of other cell types.