PATHOGENESIS OF ALLERGIC DISEASES OF THE SKIN & LUNGS

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The Allergic Diseases Center at SUNY-Stony Brook studies pathogenic mechanisms of tissue injury in a wide variety of diseases to include physically induced hives, chronic urticaria and angioedema, hereditary angioedema, Lyme disease, cryoglobulinemia (and other vasculitides) and asthma. We will study molecular mechanisms of histamine release from basophils and mast cells, activation of the classical complement pathway, and activation of the coagulation- kinin pathway, as applied to these diseases. We will develop new methods for assessment of kinin formation in human disease focusing upon cleavage of kininogen and determination of bradykinin and its degradation products. We will purify and characterize Histamine Releasing Factors(s) (HRF) which are cytokines released from lymphocytes and/or monocytes to cause basophils and mast cell degranulation and determine its relationship to histamine-releasing cytokines we have identified such as interleukin 3 and GM-CSF. We will study possible mechanisms by which a temperature change initiates histamine release in cold urticaria and the role of temperature (thermal amplitude) of cryoproteins to cause cryoprecipitation and complement activation in cryoglobulinemia. The role of neuropeptides as mediators of hives will be assessed, particularly as they pertain to cholinergic urticaria, and we will continue studies of the time course of mediator release and histologic assessment of chronic idiopathic urticaria and angioedema. The non-necrotizing perivascular inflammation of chronic urticaria will be compared to the vasculitis of cryoglobulinemia, late phase reactions, and contact dermatitis. Our assessment of hereditary angioedema will include new methods for diagnosis of the various types, assessment of Cl NIH synthesis in vitro, and identification of the vasoactive substance which causes the swelling. Lyme disease is endemic on Long Island and spreading throughout the Northeast. We propose to develop new, more accurate and specific methods of diagnosis, study immune responsiveness to B. burgdorfei, and assess its ability to activate mediator systems during infection and during Herxheimer reactions associated with therapy. Finally, we will study the interrelationship of distribution of inhaled particles in asthma with mechanical parameters such as the formation of flow-limiting segments, obstructive ventilatory parameters, and mucociliary clearance.