Tintinger Gregory R, Steel Helen C, Theron Annette J, Anderson Ronald
Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, University of Pretoria and Tshwane, Academic Division of the National Health Laboratory Service, Pretoria, South Africa.
Drug Des Devel Ther. 2009 Feb 6;2:95-104.
Unlike most other effector cells of the innate, as well as the adaptive immune systems, the neutrophil is a relatively undiscerning aggressor with scant regard for damage limitation. Although this highly combative, professional phagocyte has become increasingly implicated in the immunopathogenesis of many acute and chronic inflammatory disorders, of both infective and noninfective origin, effective pharmacological strategies to counter neutrophil aggression have remained elusive. Activation of neutrophils results in rapid mobilization of both stored and extracellular Ca(2+), resulting in abrupt, usually transient increases in cytosolic Ca(2+), which precede, and are a prerequisite for activation of the Ca(2+)-dependent pro-inflammatory activities of these cells. Mobilization of Ca(2+) by, and restoration of Ca(2+) homeostasis to activated neutrophils are multistep processes which present a number of potential targets, some well recognized and others novel and unconventional, for the pharmacological control of neutrophil-mediated inflammation. Uncovering these targets represents the primary focus of this review.
与先天性免疫系统以及适应性免疫系统的大多数其他效应细胞不同，中性粒细胞是一种相对不加区分的攻击者，很少考虑损伤限制。尽管这种极具战斗性的专业吞噬细胞越来越多地被认为与许多急性和慢性炎症性疾病的免疫发病机制有关，这些疾病既有感染性的，也有非感染性的，但对抗中性粒细胞攻击的有效药理学策略仍然难以捉摸。中性粒细胞的激活导致储存的和细胞外的Ca(2+)迅速动员，导致细胞质Ca(2+)突然、通常是短暂的增加，这在这些细胞的Ca(2+)依赖性促炎活性激活之前发生，并且是其激活的先决条件。激活的中性粒细胞对Ca(2+)的动员以及Ca(2+)稳态的恢复是多步骤过程，这为中性粒细胞介导的炎症的药理学控制提供了许多潜在靶点，其中一些是公认的，另一些是新颖的和非常规的。揭示这些靶点是本综述的主要重点。
