Cysteinyl leukotrienes mediate histamine hypersensitivity ex vivo by increasing histamine receptor numbers

Background: Hyperresponsiveness to histamine is a key feature of a variety of pathological conditions, including bronchial asthma, food allergy, colit is ulcerosa, and topical allergic disorders. Cells isolated from hyperrespo nsive individuals do not display exaggerated histamine responses ex vivo an d thus the molecular mechanisms underlying histamine responsiveness remain obscure, importantly, several in vivo observations implicate cysteinyl leuk otrienes as possible mediators of increased histamine responses. We decided to investigate whether cysteinyl leukotrienes enhance the cellular reactio n to histamine in cell types involved in pathological and immunological his tamine hyperresponsiveness, as this might provide an in vitro system for st udying histamine responsiveness and could shed light on the underlying mole cular mechanisms. Materials and Methods: Histamine responsiveness was determined by measuring histamine-induced prostaglandin E-2 production. Scatchard analysis was per formed to determine the number of histamine H-1 receptors. Mouse macrophage s, primary isolated human peripheral blood monocytes, and human umbilical s mooth muscle cells were investigated before and after cysteinyl leukotriene stimulation. Results: In all three cell types tested, cysteinyl leukotrienes instantaneo usly enhanced histamine-induced prostaglandin E-2 production. This increase in prostaglandin E-2 production coincided with the immediate and transient appearance of additional H-1 receptors on the plasma membrane. Conclusions: Cysteinyl leukotrienes prime histamine responses by recruiting additional histamine receptors in immunologically relevant cell types in v itro.