CELLULAR BASIS OF HYPERSENSITIVITY DISEASES IN HUMANS

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The program is composed of two disease-oriented subsections, pulmonary and dermatologic, which are integrated through mutual focus upon two cell types, the mast cell and the eosinophil, their products and diseases which likely result from the dys-regulation of their tissue phenotype and phlogistic potential mediated directly or via additional cell types. A particular program is to transfer the current understanding of pathobiology of bronchial asthma and its treatment to urban minority populations through a demonstration and education project with assessment of benefit. Culturally appropriate educational programs will be targeted to both patients with asthma and their personal physicians to increase their understanding of the pathobiology of this disease and the importance of objective monitoring of lung function through the use of home peak flow measurements and Health Center based spirometry. In the pulmonary subsection, the urinary excretion of LTE4 will be used as an index of the endogenous production of the cysteinyl leukotrienes in normal subjects with induced airway hyper-responsiveness and in patients with bronchial asthma as a possible index of disease activity or of distinct pathobiologic subgroups. The presence of tissue and circulating cytokines capable of altering the eosinophil phenotype so as to augment viability and prime for ligand mediated responses will be sought not only in chronic eosinophilic pneumonia but also in bullous pemphigoid. The regulation of expression of beta-glucan receptors on monocyte/macrophages in allergic bronchopulmonary aspergillosis will be assessed relative to uninfected patients and the effects of treatment with corticosteroids. Discriminatory anti-peptide antibodies and molecular probes directed against a panel of human mast cell proteases will be prepared and used to analyze mast cell maturation in vitro, utilizing insights and systems gained from parallel studies in the mouse mast cell system. Of particular note is that these probes will be used to phenotype human mast cells in normals and at normal and lesional sites of patients with physical allergies (exercise-associated anaphylaxis, cold-induced urticaria, dermographism, and cholinergic urticaria), systemic mastocytosis, and bullous pemphigoid. As the number of discriminatory probes increases, it is anticipated that the phenotyping of mast cells, along with ultrastructural analysis of granule structure and cell distribution, may reveal the pathobiologic importance of various phenotypes while also providing insight into the role of the tissue site in the regulation of phenotype.