Cell biology of macrophages role of purinergic P2X7 receptor in cell to cell communications and multinucleated giant cells formation

巨噬细胞在免疫反应和炎症反应中发挥核心作用，细胞间通讯在协调巨噬细胞反应中至关重要。巨噬细胞间细胞间通讯的一种形式包括直接的细胞间接触和巨噬细胞融合成多核巨细胞，这一分化过程与许多慢性炎性疾病有关，包括结核分枝杆菌、结节病、克罗恩病和假体植入和医疗器械的异物反应。迄今为止，细胞融合过程的机制尚不清楚。最近的证据，包括我们实验室的一些证据，暗示嘌呤能P2X7受体是炎症反应中这种分化过程的重要效应器。因此，我们的目标是阐明参与p2x7介导的多核巨细胞形成的分子和细胞生物学信号级联。除了增加我们对巨噬细胞细胞间通讯的理解外，这些研究可能为旨在干扰导致多核巨细胞形成和慢性炎症的细胞间通讯的新治疗策略提供基础。

Macrophages play a central role in immune responses and inflammatory reactions, and cell-to-cell communication is crucial in coordinating macrophage responses.One form of intercellular communication between macrophages involves direct cell-cell contact and macrophage fusion into multinucleated giant cells, a differentiation process associated with many chronic inflammatory disorders including M. Tuberculosis, sarcoidosis, Crohn's disease and foreign body reaction to implantation of prostheses and medical devices. To date, the mechanisms underlying the cell fusion process is unknown. Recent evidence including some from our laboratory, implicate the purinergic P2X7 receptor as an important effector of this differentiation process during inflammatory reactions. Our objective therefore is to elucidate the molecular and cell biology signalling cascades involved in P2X7-mediated multinucleated giant cells formation. Besides increasing our understanding of cell-to-cell communication in macrophages, such studies may provide a basis for novel therapeutic strategies aimed at interfering with intercellular communication leading to multinucleated giant cell formation and chronic inflammation.