Organophosphates Modify Eosinophil and Nerve Interaction

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DESCRIPTION (provided by applicant): Of the many suspected mediators of asthma, organophosphate (OP) pesticides such as parathion are recently implicated to cause or excacerbate asthma. OP exposure is ubiquitous and probably significant in children since OP metabolites have been reported in breast milk and children's urine. OP exposure may predispose atopic individuals to airway hyperreactivity through increased interactions of eosinophils on the airway nerves. The specific aims are to test the hypothesis that 1. OPs promote the release of major basic protien (MBP) from eosinophils leading to a loss of M2 muscarinic function and an increase in bronchoconstriction to vagal stimulation in sensitized guinea pigs, 2. OPs induce the expression of the adhesion molecules ICAM-1 and/or VCAM-1 and the chemotactant eotaxin in lung nerves, and 3. OPs induce the expression of CD11/CD18, VLA-4, and/or CCR3, the respective counerligands, on the eosinophils. Sensitized, parathion-exposed guinea pigs will be treated to block MBP and used in physiological studies to measure changes in bronchocontstriction after vagal stimulation. The observed effects of OPs on eosinophils and nerves will be measured in isolated cells.