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Mass spectrometry and metabolism of leukotriene B/sub 4/

Thesis/Dissertation ·
OSTI ID:5006443
Leukotriene B/sub 4/ (LTB/sub 4/) is a potent and powerful chemotactic factor for polymorphonuclear leukocytes and has been hypothesized to play a role as a mediator of the inflammatory response. A cell free system capable of generating leukotrienes from exogenous arachidonic acid was developed using both rat basophilic leukemia cells and murine mastocytoma cells. The cell free leukotriene generating system was used to prepare leukotrienes for mass spectral studies using electron impact (EI), chemical ionization (Cl), negative ion chemical ionization (NCl) and both positive and negative ion fast atom bombardment mass spectrometry (FAB-MS). Although all of the techniques examined yielded useful information, NCl was found to be the most useful for sensitive quantitation of leukotrienes, whereas Cl and El are more useful for unambiguous structural characterization of hydroxy fatty acid leukotrienes. Investigation of the in vivo metabolism of LTB/sub 4/ in the mouse and guinea pig indicated that less than 10% of the injected radiolabel from /sup 3/H-LTB/sub 4/ was excreted via the urine and feces. Approximately 30% of the urinary radioactivity was volatile, probably due to loss of the tritium label as water. In the monkey, approximately 10% of the injected radiolabel from /sup 14/C-LTB/sup 4/ was excreted in the urine within 5 1/2 hours. In this study, approximately 10% of the urinary radiolabel was volatile, with a large number of unidentified non-volatile products also observed. The isolated perfused rat lung was found to rapidly metabolize leukotriene C/sub 4/ to leukotrienes D/sub 4/ and E/sub 4/ and to leukotriene C/sub 4/ sulfoxide.
Research Organization:
Colorado Univ., Denver (USA). Health Sciences Center
OSTI ID:
5006443
Country of Publication:
United States
Language:
English