Pradhan D, Krahling S, Williamson P, Schlegel R A
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802, USA.
Mol Biol Cell. 1997 May;8(5):767-78. doi: 10.1091/mbc.8.5.767.
In vivo, apoptotic lymphocytes are recognized and phagocytosed by macrophages well before the final stages of DNA degradation and cell lysis. The recognition process is apparently triggered by the exposure of phosphatidylserine (PS) on the cell surface, an event which precedes cell lysis by several hours. However, multiple receptors appear to respond to this event. We demonstrate here that both activated and unactivated macrophages recognize PS, but with different receptor systems. Phagocytosis of apoptotic lymphocytes by activated (but not by unactivated) macrophages is inhibited by pure PS vesicles as well as by N-acetylglucosamine, implicating involvement of a lectin-like receptor in this case. Conversely, uptake of apoptotic lymphocytes by unactivated (but not by activated) macrophages is inhibited by PS on the surface of erythrocytes as well as by the tetrapeptide RGDS and cationic amino acids and sugars, implicating involvement of the vitronectin receptor in this case. Recognition by both classes of macrophages is blocked by the monocyte-specific monoclonal antibody 61D3. The signal recognized by activated macrophages appears to develop on the lymphocyte prior to assembly of the signal recognized by unactivated macrophages. Collectively, these results suggest that PS exposure on the surface of apoptotic lymphocytes generates a complex and evolving signal recognized by different receptor complexes on activated and unactivated macrophages.
在体内，凋亡淋巴细胞在DNA降解和细胞裂解的最后阶段之前很久就被巨噬细胞识别并吞噬。识别过程显然是由细胞表面磷脂酰丝氨酸（PS）的暴露引发的，这一事件比细胞裂解提前数小时发生。然而，多种受体似乎对这一事件做出反应。我们在此证明，活化和未活化的巨噬细胞都能识别PS，但通过不同的受体系统。纯PS囊泡以及N - 乙酰葡糖胺可抑制活化（而非未活化）巨噬细胞对凋亡淋巴细胞的吞噬作用，这表明在这种情况下有类似凝集素的受体参与。相反，红细胞表面的PS以及四肽RGDS和阳离子氨基酸及糖类可抑制未活化（而非活化）巨噬细胞对凋亡淋巴细胞的摄取，这表明在这种情况下有玻连蛋白受体参与。两类巨噬细胞的识别都被单核细胞特异性单克隆抗体61D3阻断。活化巨噬细胞识别的信号似乎在未活化巨噬细胞识别的信号组装之前就在淋巴细胞上形成。总体而言，这些结果表明凋亡淋巴细胞表面PS的暴露产生了一个复杂且不断演变的信号，该信号被活化和未活化巨噬细胞上不同的受体复合物所识别。
