來自北卡羅來那大學醫學院的研究人員發現凋亡細胞釋放ATP和UTP，它們對表達P2Y2 ATP/UTP受體的吞噬細胞來說充當一種「找到我」信號及化學引誘劑。
細胞凋亡幾乎在所有組織中都出現，是正常發育和體內平衡的構成部分。不過，即使在有較高細胞周轉率的組織中，凋亡細胞也很少見；這種現象一直被歸因於凋亡細胞具有這樣一種能力：它們能夠通過「找到我」信號的釋放來表示自己的存在，從而招來吞噬細胞，立即啟動清除過程。然而，凋亡細胞所釋放的是哪種類型的「找到我」信號以及這些信號是怎樣被吞噬細胞檢測到的仍不清楚。在這篇論文中，研究人員發現凋亡細胞釋放ATP和UTP，它們對表達P2Y2 ATP/UTP受體的吞噬細胞來說充當一種「找到我」信號及化學引誘劑。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 461, 282-286 (10 September 2009) | doi:10.1038/nature08296
Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance
Michael R. Elliott1,2, Faraaz B. Chekeni1,3, Paul C. Trampont1,2, Eduardo R. Lazarowski7, Alexandra Kadl4, Scott F. Walk1,2, Daeho Park1,2, Robin I. Woodson5, Marina Ostankovich4, Poonam Sharma4, Jeffrey J. Lysiak5, T. Kendall Harden8, Norbert Leitinger3,4 & Kodi S. Ravichandran1,2,6
1 Beirne B. Carter Center for Immunology Research,
2 Center for Cell Clearance,
3 Department of Pharmacology,
4 Robert M. Berne Cardiovascular Research Center,
5 Department of Urology,
6 Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA
7 Department of Medicine,
8 Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
Phagocytic removal of apoptotic cells occurs efficiently in vivo such that even in tissues with significant apoptosis, very few apoptotic cells are detectable1. This is thought to be due to the release of 'find-me' signals by apoptotic cells that recruit motile phagocytes such as monocytes, macrophages and dendritic cells, leading to the prompt clearance of the dying cells2. However, the identity and in vivo relevance of such find-me signals are not well understood. Here, through several lines of evidence, we identify extracellular nucleotides as a critical apoptotic cell find-me signal. We demonstrate the caspase-dependent release of ATP and UTP (in equimolar quantities) during the early stages of apoptosis by primary thymocytes and cell lines. Purified nucleotides at these concentrations were sufficient to induce monocyte recruitment comparable to that of apoptotic cell supernatants. Enzymatic removal of ATP and UTP (by apyrase or the expression of ectopic CD39) abrogated the ability of apoptotic cell supernatants to recruit monocytes in vitro and in vivo. We then identified the ATP/UTP receptor P2Y2 as a critical sensor of nucleotides released by apoptotic cells using RNA interference-mediated depletion studies in monocytes, and macrophages from P2Y2-null mice3. The relevance of nucleotides in apoptotic cell clearance in vivo was revealed by two approaches. First, in a murine air-pouch model, apoptotic cell supernatants induced a threefold greater recruitment of monocytes and macrophages than supernatants from healthy cells did; this recruitment was abolished by depletion of nucleotides and was significantly decreased in P2Y2 -/- (also known as P2ry2 -/-) mice. Second, clearance of apoptotic thymocytes was significantly impaired by either depletion of nucleotides or interference with P2Y receptor function (by pharmacological inhibition or in P2Y2 -/- mice). These results identify nucleotides as a critical find-me cue released by apoptotic cells to promote P2Y2-dependent recruitment of phagocytes, and provide evidence for a clear relationship between a find-me signal and efficient corpse clearance in vivo.