leukotriene

Leukotrienes are potent inflammatory mediators synthesized from arachidonic acid through the 5-lipoxygenase (5-LOX) pathway, primarily in leukocytes, mast cells, and eosinophils. The pathway begins when phospholipase A2 releases arachidonic acid from membrane phospholipids. 5-LOX converts arachidonic acid to 5-HPETE, then to leukotriene A4 (LTA4). LTA4 is subsequently converted to either LTB4 (via LTA4 hydrolase) or to cysteinyl leukotrienes LTC4, LTD4, and LTE4 (via LTC4 synthase). LTB4 is a powerful neutrophil chemoattractant and activator, promoting inflammation and tissue damage. The cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent bronchoconstrictors, 100-1000 times more potent than histamine, and increase vascular permeability and mucus secretion. These effects are mediated through specific G-protein coupled receptors (BLT1/2 for LTB4, CysLT1/2 for cysteinyl leukotrienes). Clinically, leukotrienes are central to asthma pathophysiology, particularly in aspirin-exacerbated respiratory disease (AERD), and are therapeutic targets for drugs like zileuton (5-LOX inhibitor) and montelukast/zafirlukast (CysLT1 receptor antagonists).