Endothelial cell recognition and phagocytosis of apoptotic lymphocytes.

摘要

Cells induced to undergo apoptosis are recognized and phagocytosed by resident tissue cells. Phagocytic clearance of apoptotic cells by macrophages and other tissue cells provides a rapid, non-inflammatory mechanism for the disposal of apoptotic cells, thereby promoting tissue homeostasis. Our laboratory has previously demonstrated that murine high endothelial venule (HEV) cells phagocytose apoptotic leukocytes in vivo and in vitro . We hypothesized that human HEV cells also phagocytose apoptotic leukocytes. In vitro, primary human HEV cells ingested gamma-irradiated human tonsil lymphocytes as compared to control lymphocytes. Thus, human HEV cells may play a role in the removal of apoptotic lymphocytes from the vasculature and, therefore, prevent damage to the vasculature and prevent the trafficking of apoptotic cells into the lymph nodes.; The linkage between apoptotic membrane and nuclear changes has been largely unexplored in primary cells. Therefore, we examined multiple apoptotic parameters in relation to caspase signaling in spontaneously dying murine spleen cells and gamma-irradiated spleen cells using peptide caspase inhibitors. The results demonstrated that DNA degradation resulting from a pro-apoptotic stimulus in primary spleen cells occurred by caspase-dependent mechanism, regardless of the method used to induce apoptosis. In contrast, membrane changes in apoptotic spleen cells occurred by caspase-independent mechanisms.; Cell surface membrane alterations on apoptotic cells are important during apoptosis because they allow for the exposure of ligands that are recognized by various phagocytes. We have found that murine endothelial cell lines express a novel receptor that mediates phagocytosis independent of phosphatidylserine recognition. This receptor, designated as the fucoidin receptor, recognizes apoptotic but not control or necrotic cells. Importantly, endothelial cell ingestion of apoptotic cells is promoted by apoptotic lymphocyte CD44 and alpha 4 integrin. This function has not been previously described for these adhesion molecules. Furthermore, apoptotic lymphocytes had increased cell surface exposure of fucoidin-like epitopes that may mediate fucoidin receptor-dependent phagocytosis. Candidate cell surface proteins expressing these fucoidin-like structures were evident. Therefore, we conclude that apoptotic lymphocytes display novel fucosylated carbohydrate epitopes in addition to cell surface lipid changes. In summary, fucoidin-receptor mediated phagocytic clearance may represent a component of a multi-recognition system that ensures clearance of apoptotic cells.