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. Increasing evidence suggests that histamine also regulates the function of inflammatory and immune cells. Macrophages are primarily involved in inflammatory diseases of the lung. We explored the ability of low concentrations of histamine 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 incubated (37 degrees C, 2-24 h) with histamine (10(-9)-10(-6) M). At the end of incubation, the release of beta-glucuronidase and IL-6 was determined.


RESULTS
Histamine induced a concentration-dependent release of beta-glucuronidase and IL-6 with a maximum release after 2 and 6 h of incubation, respectively. Exocytosis induced by histamine was noncytotoxic and was Ca(2+)- and temperature-dependent. The effect of histamine was inhibited by the H(1) receptor antagonist fexofenadine but not by the H(2) antagonist ranitidine.


CONCLUSIONS
These data indicate that histamine is an effective stimulus for exocytosis and cytokine production from human lung macrophages. These effects are inhibited by pharmacological concentrations of fexofenadine. Our results suggest that histamine may contribute to the long-term evolution of lung inflammation and tissue remodelling in allergic diseases by modulating the production of proinflammatory and immunoregulatory mediators by macrophages.
Marone
G
G
Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy. marone@unina.it
Gentile
M
M
Petraroli
A
A
De Rosa
N
N
Triggiani
M
M
D002478:Cells, Cultured; D005089:Exocytosis; D005966:Glucuronidase / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D015850:Interleukin-6; D016593:Terfenadine; D006632:Histamine; C093230:fexofenadine; D005966:Glucuronidase