Date of Award

12-1995

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Leonard J. Beuving

Second Advisor

Dr. William F. Jackson

Third Advisor

Dr. Charles D. Mackenzie

Fourth Advisor

Dr. Robert R. Eversole

Access Setting

Masters Thesis-Open Access

Abstract

Leukotriene (LT) C4 is a potent myotropic product of arachidonic acid 5-lipoxygenation that is thought to play a role in the pathophysiology of immediate hypersensitivity reactions and inflammation. We designed the present study to evaluate the capacity of August (AUG) rat mixed peritoneal leukocytes to generate LTC4 when challenged with different concentrations of the Ca2+ ionophore A23187 and to test the hypothesis that LTC4 biosynthesis is regulated via a protein kinase C (PKC)-dependent mechanism. The AUG rat, which has a spontaneously high number of peritoneal eosinophils that can be harvested by a simple lavage procedure, is a potentially important animal model of eosinophilia that has not been well characterized. Our findings indicate that A23187-stimulated LTC4 biosynthesis is 5- lipoxygenase activating protein (FLAP) inhibitor-sensitive and is both Ca2+/Mg2+ - and concentration-dependent. Furthermore, LTC4 production appears to be regulated antagonistically via serine/threonine- and tyrosine-specific phosphorylation mechanisms.

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