Wódz-Naskiewicz Karolina, Pawliczak Rafał
Zakład Immunopatologii, Katedra Alergologii, Immunologii i Dermatologii, Uniwersytet Medyczny w Łodzi, Łódź, Poland.
Postepy Biochem. 2009;55(4):395-405.
Cysteinyl leukotrienes (LTC4, LTD4, LTE4) have a proinflamation effect, such as contraction of blood vessels smooth muscle and the respiratory tract, chemotaxis of proinflammatory cells increased endothelium cells permeability and mucus secretion. They are lipid mediators playing an important part in the pathophysiology of bronchial asthma, allergic rhinitis, atopic dermatitis, urticaria, cardiovascular system disorders and tumors. They act through at least four receptors from the rhodopsin gene family, lying in the area of GPCR genes superfamily--CYSLTR1, CYSLTR2, GPR17 and receptor for LTE4 (CYSLT(E)R). Their location, apart from small exceptions, is differentiated and typical for tissues. The highest CYSLTR1 expression was stated in the spleen, peripheral blood leucocytes, interstitial lung macrophage and smooth muscle cells. CYSLTR2 shows highest expression in the hearth, adrenal glands, placenta, spleen and peripheral blood leucocytes, and somewhat smaller in the brain. Biochemical and pharmacological study and the analysis of sequences have shown that all three types of receptors belong to the group of 7-transmembrane receptors--GPCR. The CYSLTR1 excitation power is distributed: LTD4>LTC4>LTF4, and CYSLTR2 LTC4=LTD4>LTE4. Cysteinyl leukotrienes receptors are coupled with the G(q/11) proteins and signal path leading to phosphatidylinositol hydrolysis (PI) and mobilization of intracellular calcium. These receptors are in vivo coupled with the PTX-sensitive G(q/11) protein or both G proteins. CYSLTR1 increases the metabolism of PI and intracellular calcium, activates MAPK kinases, induces differentiation and proliferation of cells, chemotaxis, actin reorganization, release of inflammation mediators and regulation of hematopoietic stem cells. CYSLTR2 also increases the concentration of intracellular calcium, stimulates the release of IL-8 and increases expression of early genes. It is connected to thrombosis, vessel damage, inflammation process and cell death. The existence of new, nuclear, localization of CYSLTR and coexistence with other membrane receptors is postulated. It is probable that they can crate homo- or heterodimers. This indicates the existence of new, previously not know actions of, cysteinyl leukotrienes and their receptors.
半胱氨酰白三烯（LTC4、LTD4、LTE4）具有促炎作用，如引起血管平滑肌和呼吸道收缩、促炎细胞趋化、增加内皮细胞通透性及黏液分泌。它们是脂质介质，在支气管哮喘、过敏性鼻炎、特应性皮炎、荨麻疹、心血管系统疾病及肿瘤的病理生理学中起重要作用。它们通过视紫红质基因家族的至少四种受体发挥作用，这些受体位于GPCR基因超家族区域——CYSLTR1、CYSLTR2、GPR17和LTE4受体（CYSLT(E)R）。除少数例外，它们的定位具有组织特异性。CYSLTR1在脾脏、外周血白细胞、肺间质巨噬细胞和平滑肌细胞中表达最高。CYSLTR2在心脏、肾上腺、胎盘、脾脏和外周血白细胞中表达最高，在大脑中的表达稍低。生化和药理学研究以及序列分析表明，这三种受体均属于7跨膜受体——GPCR。CYSLTR1的激动效力分布为：LTD4>LTC4>LTF4，而CYSLTR2为LTC4=LTD4>LTE4。半胱氨酰白三烯受体与G(q/11)蛋白偶联，信号通路导致磷脂酰肌醇水解（PI）和细胞内钙动员。这些受体在体内与PTX敏感的G(q/11)蛋白或两种G蛋白偶联。CYSLTR1增加PI代谢和细胞内钙，激活MAPK激酶，诱导细胞分化和增殖、趋化、肌动蛋白重组、炎症介质释放及造血干细胞调节。CYSLTR2也增加细胞内钙浓度并刺激IL-8释放，增加早期基因表达。它与血栓形成、血管损伤、炎症过程及细胞死亡有关。推测存在新的核定位的CYSLTR以及与其他膜受体的共存。它们可能形成同二聚体或异二聚体。这表明半胱氨酰白三烯及其受体存在新的、以前未知的作用。
