Immunohistochemical localization of histamine-stimulated increases in cyclic GMP in guinea pig lung

Abstract

A significant number of asthmatic subjects are provoked by allergic reactions. The underlying pathophysiologic event is mast cell degranulation with the release and generation of the mediators of anaphylaxis. Histamine, one of the major mast cell mediators, causes 10- to 50-fold increases in guinea pig lung cyclic 3',5'-guanosine monophosphate (cyclic GMP) through H1 receptor stimulation. Employing monoclonal antibodies directed at cyclic GMP, immunocytochemical techniques were used to identify those specific cells in lung responding to histamine stimulation with increases in cyclic GMP. The most responsive cells were alveolar and parenchymal macrophages, pleural lining cells, and endothelial and epithelial cells. Little or no increases in bronchial or vascular smooth muscle cyclic GMP was noted. At the height of the reaction, a generalized increase in cyclic GMP staining of all alveolar cells was observed. These findings suggest that the lining cells of the lung including macrophages, mesothelial, endothelial, and epithelial cells may be the most responsive cells to histamine released during allergic responses. The absence of muscular staining suggests that cyclic GMP does not participate in histamine-stimulated muscle contraction.