Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response.

TLDR

Leukotrienes B4, C4, and D4, derived from arachidonic acid, are potent modulators of microvascular function, as demonstrated in the hamster cheek pouch model. Topical application of leukotrienes C4 and D4 produced brief, angiotensin‑like arteriolar constriction followed by dose‑dependent plasma leakage from postcapillary venules, whereas leukotriene B4 did not cause vasoconstriction or leakage but induced reversible leukocyte adhesion, underscoring leukotrienes’ role in acute inflammatory microcirculatory changes.

Abstract

Leukotrienes B4, C4, and D4, members of a recently discovered family of substances biosynthesized from arachidonic acid, were found to have potent microvascular actions in the hamster cheek pouch. When applied topically to the vascular network, leukotrienes C4 and D4 caused an intense constriction of arterioles, being similar to angiotensin in potency in this respect. The vasoconstriction induced by leukotrienes C4 and D4 was short-lived, and it was consistently followed by a marked and dose-dependent extravasation of macromolecules from postcapillary venules. Histamine did not constrict arterioles, but it elicited leakage of plasma, although on a molar basis it was no more than 1/1000th as potent as the leukotrienes. When used in the same concentration range as leukotrienes C4 and D4, leukotriene B4 did not evoke vasoconstriction or promote plasma leakage. On the other hand, leukotriene B4 caused a conspicuous and reversible adhesion of leukocytes to the endothelium in postcapillary venules. Our findings that leukotrienes induce microcirculatory alterations in vivo, closely resembling the early events in the acute inflammatory response, imply that leukotrienes, formed in several blood-borne and tissue-bound cells, may mediate important microcirculatory adjustments to noxious stimuli.