Alterations in Cell Surface Phosphatidylserine and Sugar Chains during Apoptosis and Their Time-Dependent Role in Phagocytosis by Macrophages.

Abstract

Apoptosis, or programmed cell death, is a process crucial in organ development and homeostasis. Apoptotic cells are fragmented and form so-called apoptotic bodies that are engulfed and degraded by neighboring phagocytes. In order to engulf apoptotic cells, receptors on the phagocytes must recognize ligands expressed exclusively on apoptotic cells. Apoptosis induces several cellular changes, including membrane blebbing, condensation of chromatin along the nuclear membrane, and the generation of membrane-enclosed apoptotic bodies.1,2) In addition, specific changes in cell surface molecules have been observed during apoptosis, including the expression of phosphatidylserine (PS) and certain proteins, and changes in the sugar chains of glycoproteins and glycolipids. [3][4][5][6][7][8] These changes contribute to a number of different biological functions, in particular, phagocyte recognition and ingestion of apoptotic cells.Recently, many cell surface molecules, such as PS and sugar chains, have been reported to function in phagocyte recognition of apoptotic cells. [9][10][11][12][13][14] PS, which is normally restricted to the inner leaflet of the plasma membrane, becomes exposed on the outer leaflet of apoptotic cells, and changes in the pattern of glycosylation of cell surface glycoproteins and glycolipids also occur. Recognition of apoptotic cells is mediated by a variety of phagocytic receptors including lectins, scavenger receptor A (SR-A), and CD36 in conjunction with the vitronectin receptor. Ligands on apoptotic cells that are recognized by these receptors include sugars, PS, and surface-bound thrombospondin (TSP). However, this process is a cooperative interaction between several cell-recognizing molecules, not just a single molecule, and how these molecules work cooperatively during the process of phagocytosis remains uncertain. Thus, we estimated the changes in PS and sugar chains during apoptosis and studied several factors concerned with the phagocytosis of apoptotic cells in each of three phases, which were defined by changes in cell surface molecules. Although several researchers have studied this mechanism, most have been concerned with blood cells, such as lymphocytes; thus, the mechanism in epithelial cells has not been examined thoroughly. We used cells of the human colon adenocarcinoma cell line HT-29 as apoptotic cells and phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells as macrophages to study the mechanisms of phagocytosis of apoptotic cells. Apoptotic cells are effectively ingested and removed by phagocytes. This process is dependent on specific recognition by phagocytes of ligands expressed exclusively on apoptotic cells. These ligands, cell surface molecules such as phosphatidylserine (PS), altered sugar chains, and the thrombospondin-binding domain, are expressed following the induction of apoptosis. However, they are not expressed simultaneously, and each factor seems to have a respective role in different phases of apoptosis. In this paper, we classified the apoptotic process in...

Decrease of sialic acid residues as aneat-mesignal on the surface of apoptotic lymphocytes

“…Changes in the glycomic profile of apoptotic cells have previously been studied by various groups, who have analyzed cells of different origin (Azuma et al, 2002;Hart et al, 2000;Rapoport and Pendu, 1999). In these previous studies, both an increase and a decrease of membrane-bound Sias have been reported, depending on the cell type under investigation.…”

Phagocytosis of apoptotic cells: a matter of balance

“…Sialic acids are ubiquitously expressed at the nonreducing ends of oligosaccharide chains and are important in various biological events. During apoptosis they can be enzymatically removed to expose asialoglycoconjugates, which are relevant in inducing phagocytosis [39][40][41].…”

Identification of Apoptotic Cells by Means of Lectin Histochemistry: State of the Art Review

“…In 2000, a lectin-based approach for detecting apoptotic cells in flow cytometry detected a changed pattern of glycoproteins of the plasma membrane during apoptosis using the FITC-labeled lectin Narcissus pseudonarcissus (NPn) [53]. In 2004, application of the same using a flow cytometric procedure showed that apoptosis is associated with a marked decrease in cell surface sialylation.…”