Chromatin-Independent Binding of Serum Amyloid P Component to Apoptotic Cells

Abstract

Human serum amyloid P component (SAP) is a glycoprotein structurally belonging to the pentraxin family of proteins, which has a characteristic pentameric organization. Mice with a targeted deletion of the SAP gene develop antinuclear Abs, which was interpreted as evidence for a role of SAP in controlling the degradation of chromatin. However, in vitro SAP also can bind to phosphatidylethanolamine, a phospholipid which in normal cells is located mainly in the inner leaflet of the cell membrane, to be translocated to the outer leaflet of the cell membrane during a membrane flip-flop. We hypothesized that SAP, because of its specificity for phosphatidylethanolamine, may bind to apoptotic cells independent of its nuclear binding. Calcium-dependent binding of SAP to early, nonpermeable apoptotic Jurkat, SKW, and Raji cells was indeed observed. Experiments with flip-flopped erythrocytes confirmed that SAP bound to early apoptotic cells via exposed phosphatidylethanolamine. Binding of SAP was stronger to late, permeable apoptotic cells. Experiments with enucleated neutrophils, with DNase/RNase treatment of late apoptotic Jurkat cells, and competition experiments with histones suggested that binding of SAP to late apoptotic cells was largely independent of chromatin. Confocal laser microscopic studies indeed suggested that SAP bound to these apoptotic cells mainly via the blebs. Thus, this study shows that SAP binds to apoptotic cells already at an early stage, which raises the possibility that SAP is involved in dealing with apoptotic cells in vivo.

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

“…SAP shows specific binding to DNA, nuclear chromatin, chromatin-presenting surfaces of apoptotic cells, and nuclear components accessible as a result of necrosis (2,23). The amount of SAP bound by late apoptotic cells is at least 1 order of magnitude higher that that bound by early apoptotic cells (24). Defective handling of chromatin (e.g., released by primarily necrotic cells or apoptotic cells undergoing secondary necrosis), as well as deficient opsonization, recognition, and removal of early and late apoptotic cells, can contribute to the development of autoimmune symptoms (7,25).…”

Serum amyloid P component binds to late apoptotic cells and mediates their uptake by monocyte‐derived macrophages

“…C1q therefore seems essential for the adequate uptake of apoptotic cells by macrophages. However, other complement components, such as C3 and C4, and the pentraxins C-reactive protein (CRP), serum amyloid P component (SAP), and PTX3 also bind to apoptotic cells and mediate their uptake by macrophages (8,9).…”

Dietary modulation and structure prediction of rat mucosal pentraxin (Mptx) protein and loss of function in humans

“…There, similar to SAP and CRP [17,20], it may be involved in binding and clearance of dying cells. Possibly, Mptx binds specifically to apoptotic epithelial cells, similar to SAP [10], and mediates their clearance as part of the normal cell turnover processes in healthy colonic mucosa. Alternatively, Mptx may be involved in the normal regulation of apoptosis.…”