This broad-based project is designed to explore pathophysiologic mechanisms responsible for allergic diseases. During the past year, the following observations have been made: The identification of cells responding to isoproterenol with increases in cyclic AMP in guinea pig lung has been described. The presence of an inhibitor of histamine N-methyltransferase in plasma obtained from patients in septic shock has been described and the plasma levels of histamine in sepsis determined; septic plasma has normal histamine. The sequence of events in allergy skin testing has been determined, including definition of the morphology of cutaneous mast cell degranulation and concomitant changes in plasma histamine. The major clinical response to mast cell mediators is increased vascular permeability in response to mediators, neurogenic inflammation, and late phase allergic responses have been explored. A molecule released from neutrophils which is capable of causing mast cell degranulation has been discovered and named HRA-N. HRA-N is 140C-2400 daltons, heat stable, active in vivo and in vitro, and may play a role in the generation of late phase allergic reactions. Tracheal aspirates of children with bronchopulmonary dysplasia have been found to be relatively deficient in lactoferrin, while having the same levels of histamine, albumin, and total protein as controls with hyaline membrane disease. This observation has potential importance in early identification of BPD-prone infants. Finally, the disease cataneneal anaphylaxis has been described and a treatment developed.
