Our analysis of events in immediate hypersensitivity have focused upon several major areas: 1) Analysis of mast cell morphology during degranulation showing regional differences between skin and either lung or nasal mast cells. 2) Mast cell secretagogues, particularly neurogenic or inflammatory derived. Sensory stimulation leads to release of neuropeptides and increased vascular permeability. This neurogenic inflammation is largely independent of mast cell activation but can involve mast cells if prolonged in duration. Conversely, neutrophils spontaneously release a factor known as histamine releasing factor (HRA-N) which causes mast cells and basophils to release mediators. This factor may be relevant to recruiting mast cells to participate in inflammatory reactions. 3) Mast cell mediators and their capacity to cause allergic disease. Histamine causes dramatic increases in lung cyclic GMP, localized to macrophages, epithelial and endothelial cells initially and followed by diffuse lung increases in cyclic GMP. Bronchial smooth muscle, however, is largely uninvolved. Histamine can be measured in venous plasma during delayed vibratory angioedema after cold urticaria and after routine allergy skin testing. 4) Modulation of allergic reactions. The capacity of LHRH analogue to modify progesterone-related anaphylaxis and the capacity of ketotifen to reduce exercise anaphylaxis are being studied in separate blinded protocols. These studies are helping to unravel the pathophysiologic events occurring during allergic diseases and will provide insights into improved therapy.
