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, colitis ulcerosa, and topical allergic disorders. Cells isolated from hyperresponsive individuals do not display exaggerated histamine responses ex vivo and thus the molecular mechanisms underlying histamine responsiveness remain obscure. Importantly, several in vivo observations implicate cysteinyl leukotrienes as possible mediators of increased histamine responses. We decided to investigate whether cysteinyl leukotrienes enhance the cellular reaction to histamine in cell types involved in pathological and immunological histamine hyperresponsiveness, as this might provide an in vitro system for studying histamine responsiveness and could shed light on the underlying molecular mechanisms.


METHODS
Histamine responsiveness was determined by measuring histamine-induced prostaglandin E(2) production. Scatchard analysis was performed to determine the number of histamine H(1) receptors. Mouse macrophages, primary isolated human peripheral blood monocytes, and human umbilical smooth muscle cells were investigated before and after cysteinyl leukotriene stimulation.


RESULTS
In all three cell types tested, cysteinyl leukotrienes instantaneously 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 vitro.
Pynaert
G
G
Department for Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, Ghent, Belgium.
Grooten
J
J
van Deventer
S J
SJ
Peppelenbosch
M P
MP
D000818:Animals; D001769:Blood; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media; D003545:Cysteine / Q000737:chemistry*; D015232:Dinoprostone / Q000096:biosynthesis; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015289:Leukotrienes / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011969:Receptors, Histamine H1 / Q000096:biosynthesis / Q000378:metabolism*
D003470:Culture Media; D006633:Histamine Antagonists; D015289:Leukotrienes; D011969:Receptors, Histamine H1; D006632:Histamine; D015232:Dinoprostone; D003545:Cysteine