Histamine-induced activation of human lung macrophages

Background: Histamine plays a central role in the pathogenesis of allergic and inflammatory diseases by modulating vascular and airway responses. Incr easing evidence suggests that histamine also regulates the function of infl ammatory and immune cells. Macrophages are primarily involved in inflammato ry diseases of the lung. We explored the ability of low concentrations of h istamine to induce the release of proinflammatory mediators from human lung macrophages. Methods: Macrophages purified (>95%) from lung parenchyma by Percoll density gradients and adherence to polystyrene dishes were incubate d (37 degreesC, 2-24 h) with histamine (10(-9)-10(-6) M). At the end of inc ubation, the release of beta -glucuronidase and IL-6 was determined. Result s: Histamine induced a concentration-dependent release of beta -glucuronida se and IL-6 with a maximum release after 2 and 6 h of incubation, respectiv ely. Exocytosis induced by histamine was noncytotoxic and was Ca2+- and tem perature-dependent. The effect of histamine was inhibited by the H-1 recept or antagonist fexofenadine but not by the H-2 antagonist ranitidine. Conclu sions: These data indicate that histamine is an effective stimulus for exoc ytosis and cytokine production from human lung macrophages. These effects a re inhibited by pharmacological concentrations of fexofenadine. Our results suggest that histamine may contribute to the long-term evolution of lung i nflammation and tissue remodelling in allergic diseases by modulating the p roduction of proinflammatory and immunoregulatory mediators by macrophages. Copyright (C) 2001 S. Karger AG. Basel.