Phospholipid signaling from apoptotic cells

炎症之后，不必要的和受损的细胞的凋亡是组织修复和修复的基本过程。专业或非专业吞噬细胞吞噬和回收凋亡细胞，导致它们在有害的细胞内内容物分散之前被清除，并积极抑制炎症。事实上，吞噬缺陷与自身免疫和过度活跃的炎症有关。越来越多的证据表明，凋亡细胞的磷脂(Pls)是吞噬细胞募集、识别和非炎性吞噬的重要信号。与大多数其他调解人不同，请注意 立即可用，但要么是潜伏的(例如，必须外化的磷脂酰丝氨酸(GPSer))，要么可以进行“经济”修饰，以有效地发出细胞死亡的信号。几乎总是存在于细胞凋亡和/或重塑磷脂酶(PLA2)的氧化剂对PL的修饰被认为是为了产生PL信号。利用灵敏的质谱学技术，提出了吸引吞噬细胞的主要候选者 释放溶血磷脂酰胆碱(Lyso-GPCho)、血小板激活因子(PAF)和溶血磷脂酰胆碱(Lyso-GPSer)。在质膜外叶中几乎普遍出现GPSer物种是由于氨基磷脂转位酶(APLT)失活和激活的PL触发器，虽然需要GPSer来识别，但它不足以驱动吞噬细胞的吞噬。GPSer的种类尚未定义，有证据表明，氧化剂的修饰对这一过程至关重要。初步数据表明，在细胞凋亡过程中都会产生sn-2和sn-1 lyso-GPSer。越来越多的数据支持这一假设，即Lyso-pls是钙离子通量的信号转导信号，因此被认为是驱动PL触发器并抑制凋亡细胞中的APLT(由流式细胞仪研究的脂质运动确定)。对于这些用于识别凋亡细胞的PL信号的提炼、呈现或释放的身份或机制，我们知之甚少。逐步地，假设：i)氧化剂和/或在凋亡过程中PLA2的激活导致信号GPCho和GPSer物种的细化，ii)APLT活性的丧失和激活的PL触发器使它们在血浆中移动 在某种程度上是由PL物种本身驱动的膜，以及iii)它们释放到介质中，或保留在细胞表面的吞噬信号以进行吞噬募集和非炎症性吞噬。

Following inflammation, apoptosis of unnecessary and damaged cells is a fundamental process of tissue restoration and repair. Engulfment and recycling of apoptotic cells by either professional or non-professional phagocytes results in their removal before noxious intracellular contents are dispersed, and actively suppresses inflammation. Indeed, defects in engulfment are linked to autoimmunity and over-exuberant inflammation. Increasing evidence suggests that phospholipids (PLs) of apoptosing cells serve as important signals for the recruitment, recognition and non-phlogistic engulfment by phagocytes. Unlike most other mediators, PLs are immediately available, but either latent (e.g phosphatidylserine (GPSer) which must be externalized), or can be "economically" modified to effectively signal the cell's demise. PL modification by oxidants, almost always present in apoptosis, and/or by remodeling phospholipases (PLA2s) is hypothesized to generate signaling PLs. Using sensitive mass spectrometry techniques, leading candidates for the attraction of phagocytes are proposed to be released lyso-phosphatidylcholine (lyso-GPCho), platelet activating factor (PAF), and lyso-GPSer species as well. The near-universal appearance of GPSer species in the plasma membrane outer leaflet results from inactivation of an aminophospholipid translocase (APLT) and activated PL flip-flop, and while GPSer is required for recognition, it is insufficient to drive phagocyte engulfment. Species of GPSer have not been defined and there is evidence that modification by oxidants is critical to the process. Preliminary data shows that both sn-2 and sn-1 lyso-GPSer are produced during apoptosis. Mounting data support the hypothesis that lyso-PLs signal for calcium flux, and as such, are hypothesized to drive PL flip-flop and inhibit the APLT in apoptosing cells (determined by lipid movements investigated by flow cytometry). Little is known of the identities or mechanisms of elaboration, presentation or release of these PL signals for apoptotic cell recognition. Stepwise, it is hypothesized that ; i) oxidants and/or activation of PLA2s during apoptosis result in elaboration of signaling GPCho and GPSer species, ii) loss of APLT activity and activated PL flip-flop moves them across the plasma membrane in a manner that is, in part, driven by the PL species themselves, and iii) their release to the media, or retention on the surface of the apoptosing cell signals for phagocytic recruitment and non-phlogistic engulfment.