Mast cell chymase potentiates histamine-induced wheal formation in the skin of ragweed-allergic dogs.

Abstract

Skin mast cells release the neutral protease chymase along with histamine during degranulation. To test the hypothesis that chymase modulates histamine-induced plasma extravasation, we measured wheal formation following intradermal injection of purified mast cell chymase and histamine into the skin of ragweed-allergic dogs. We found that chymase greatly augments histamine-induced wheal formation. The magnitude of the potentiating effect increases with increasing doses of chymase and becomes maximal -30 min after administration. Injection of chymase without histamine does not evoke wheal formation. The chymase potentiation of histamine-induced skin responses is prevented completely by pretreatment with the HI-receptor antagonist pyrilamine, and is prevented by inactivation of chymase with soybean trypsin inhibitor, suggesting that both histamine and preserved catalytic activity are required for the effects of chymase. To examine the effects of histamine and chymase released in situ in further experiments, we measured wheal size following local degranulation of mast cells by intradermal injection of ragweed antigen or compound 48/80. We found that pretreatment with either soybean trypsin inhibitor or pyrilamine markedly reduces ragweed antigen-or 48/80-induced wheal formation, supporting the results obtained by injection of exogenous chymase and histamine. These findings suggest a novel and important proinflammatory role for chymase in modulating the effects of histamine on vascular permeability during mast cell activation. (J. Clin. Invest. 1990. 86:555-559.) Key words: protease * immediate hypersensitivity * vascular permeability

Human Chymase Expression in a Mice Induces Mild Hypertension with Left Ventricular Hypertrophy

“…Isolated chymase activates a potent proinflammatory cytokine, interleukin (IL)-1β (14), degrades IL-4 (15), and cleaves a membrane-bound stem cell factor, provoking its release from cells (16). Isolated dog chymase is known to enhance histamine-induced vascular leakage in the skin of dogs (17). Human mast cell chymase also induces neutrophil and eosinophil recruitment in the skin of guinea-pigs as well as in the peritoneum of mice (18), suggesting a potential role of h-chymase in inflammatory cell migration.…”

Distribution, density and heterogeneity of canine mast cells and influence of fixation techniques

“…The involvement of specific mast cell subtypes and mast cell proteases in the pathogenesis of disease (Harvima IT et al 1993;Rubinstein I et al 1990;Sekizawa K et al 1989;Su M et al 1993) underlines the importance of a more detailed study on canine mast cell heterogeneity. Our intention was to gather species-specific data on mast cell density in different organs and tissue locations, on heterogeneity based on their protease content and on the relative distribution of mast cell subtypes under different fixation conditions.…”

Enzymatic Modulation of Bronchoconstriction, Gland Secretion, Plasma Extravasation and Cough.

“…Chymase potentiated histamine-induced wheal formation in the skin of ragweed-allergic dogs and this effect of chymase was completely inhibited by soybean trypsin inhibitor, an active site inhibitor of dog chymase (Rubinstein et al 1990b). Because chymase and histamine are released together from mast cells in the skin, chymase may have a pathophysiological role in inflammatory responses in the skin by the augmentation of plasma extravasation induced by histamine.…”