Leukotrienes (LTs) are potent proinflammatory mediators, and many important aspects of innate and adaptive immune responses are regulated by LTs. Key members of the LT synthesis pathway are overexpressed in adipose tissue (AT) during obesity, resulting in increased LT levels in this tissue. We observed that several mouse adipocyte cell lines and primary adipocytes from mice and humans both can ...

Two classes of arachidonic acid derivatives can be formed by two distinct enzyme systems. Cyclo-oxygenases synthesise prostaglandins, prostacyclin and thromboxane A2 which all possess both pro- and anti-inflammatory properties. Lipoxygenases synthesise on the one hand chemotactic factors, the hydroxylated derivatives of arachidonic acid, the most powerful of which is leukotriene B4, and on the ...

Leukotrienes are novel mediators derived from arachidonic acid through the 5-lipoxygenase enzyme system. Leukotriene B4 has potent effects on leukocyte function and in vivo induces leukocyte accumulation and changes in vascular permeability and modulates pain responses. Peptidolipid leukotrienes are potent smooth muscle-contracting agents. They may have important cardiovascular actions through ...

During the last 25 years prostaglandins and, more recently, leukotrienes have commanded increasing interest in the field of medical research. The identification of these substances as potent local hormones which contribute to many physiological and pathological processes has made them the target for potential new therapies. An understanding of the origin of prostaglandins and leukotrienes has l...

Cysteinyl-leukotrienes, i.e. leukotriene (LT) C4, D4 and E4, are inflammatory mediators and potent airway- and vasoconstrictors. Two different cysteinyl-leukotriene receptors have been cloned, CysLT1 and CysLT2. This report reviews recent data on CysLT receptor characterisation as well as studies of modulatory mechanisms involved in cysteinyl-leukotriene-induced responses. On the basis of funct...

The seven-transmembrane G protein-coupled receptors activated by leukotrienes are divided into two subclasses based on their ligand specificity for either leukotriene B(4) or the cysteinyl leukotrienes (LTC(4), LTD(4), and LTE(4)). These receptors have been designated BLT and CysLT receptors, respectively, and a subdivision into BLT(1) and BLT(2) receptors and CysLT(1) and CysLT(2) receptors ha...

Inhalation of antigen in immunized mice induces an infiltration of eosinophils into the airways and increased bronchial hyperreactivity as are observed in human asthma. We employed a model of late-phase allergic pulmonary inflammation in mice to address the role of leukotrienes (LT) in mediating airway eosinophilia and hyperreactivity to methacholine. Allergen intranasal challenge in OVA-sensit...

Isolated dog mastocytoma cells sensitized with dog anti-ragweed IgE and challenged with ragweed antigen or incubated with ionophore A23187 or the carboxy-terminal dodecapeptide of platelet factor 4, PF4(59-70), release histamine and concurrently generate leukotrienes B4, C4, and D4. In contrast, the exposure of mastocytoma cells to 0.1-3 micrograms/ml of 15-hydroxyeicosatetraenoic acid (15-HETE...

The diameters of pial arterioles of mice were monitored in vivo with an image-splitting technique and television microscopy. Concentrations of leukotriene C4 as low as 10(-7) M constricted the arterioles. The leukotriene C4-D4 receptor blocker ICI 198615 (10(-8) M) inhibited the response. Endothelial injury by helium-neon laser/Evans blue technique eliminated the constriction and unmasked a sli...