Degree Type

Dissertation

Date of Award

1986

Degree Name

Doctor of Philosophy

Department

Theses & dissertations (Interdisciplinary)

Major

Immunobiology

First Advisor

James A. Roth

Abstract

Treatment of cattle with the potent glucocorticoid, dexamethasone, results in a suppression of neutrophil iodination, oxidative metabolism, antibody-dependent cell-mediated cytotoxicity (ADCC) and an enhancement of random migration. In order to determine what role arachidonic acid metabolism may play in these phenomena, neutrophils from both nontreated and dexamethasone-treated cattle were labeled with [superscript]14C-arachidonic acid, stimulated with opsonized zymosan and the changes in arachidonic acid metabolism determined. It was found that stimulated bovine neutrophils release arachidonic acid, primarily from the phospholipids, and produce two lipoxygenase products, leukotriene B4 and 5-hydroxyeicosatetraenoic acid. In vivo treatment with dexamethasone significantly lowered the amount of arachidonic acid released and metabolites formed. Treatment of normal neutrophils in vitro with two lipoxygenase inhibitors revealed that neutrophil iodination and oxidative metabolism are inhibited when the lipoxygenase pathway is suppressed, but ADCC and random migration are unaltered. Indomethacin, a cyclooxygenase inhibitor, had no effect on the arachidonic acid metabolism or on any of the functions. It was concluded that dexamethasone-treatment acts to alter bovine neutrophil arachidonic acid metabolism but this alteration cannot explain all the changes in neutrophil function seen with glucocortoid treatment. The use of the immunomodulator, tuftsin, as a potential antagonist for the effects of dexamethasone on bovine neutrophils was evaluated. Tuftsin was added in vitro to neutrophils from nontreated and dexamethasone-treated cattle and was administered in vivo to normal and dexamethasone-treated cattle and the neutrophil functions evaluated. Neutrophil iodination and ingestion were enhanced by in vitro tuftsin treatment of normal bovine neutrophils while in vitro treatment of neutrophils from dexamethasone-treated cattle had no effect. In vivo tuftsin treatment showed only marginal effects on neutrophil ADCC, iodination and cytochrome C reduction. However, when both tuftsin and dexamethasone were administered in vivo, there was significant reversal of the dexamethasone induced alterations in neutrophil random migration and iodination. The ADCC response was also enhanced, but not significantly. Because of these actions, tuftsin may be useful in reversing some of the suppressive effects of glucocorticoids on the immune system.

DOI

https://doi.org/10.31274/rtd-180813-2229

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Deborah Su Ann Webb

Language

en

Proquest ID

AAI9020130

File Format

application/pdf

File Size

98 pages

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