Effects of antiplatelet agents on polymorphonuclear leukocytes exposed to mechanical trauma

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dc.contributor.advisorMcIntire, Larry V.
dc.contributor.committeeMemberHellums, Jesse D.
dc.contributor.committeeMemberMartin, R. Russell
dc.creatorRothberg, Jeanne Mays
dc.date.accessioned2018-12-18T21:18:14Z
dc.date.available2018-12-18T21:18:14Z
dc.date.issued1981
dc.description.abstractThe effects of shear stress on polymorphonuclear leukocytes (PMNs) were investigated to ascertain whether mechanical trauma induces lysosomal granule release or membrane lysis. In addition, the effects of antiplatelet agents on PMN leukocyte response to shear stress were studied. The antiplatelet agents, known to elevate intracellular and cyclic adenosine monophosphate (cAMP), included the following: prostaglandin Ej (PGEi), prostaglandin I2 (PGI2), theophylline, RA-8 (dipyridamole), and the dipyridamole analog, RA-233. PMN leukocyte suspensions were exposed to shear stresses of 1 or 3 dynes/cm2 at room temperature (23°C) for 1 minutes. Leukocyte responses were monitored by the following measurements. The electronic particle count was measured to indicate shear-induced aggregation and lysis. 8-Glucuronidase in the extracellular fluid was assayed to indicate azurophilic granule release. Finally, lactic dehydrogenase release was measured to indicate cell lysis due to PMN exposure to shear stress. Results of the shear-induced effects on PMNs without drug treatment show that cell loss, granule release, and cell lysis increase with increasing shear stress. Furthermoré, PMNs exposed to a shear stress of 1 dynes/cm2 release approximately equal percentages of 3-glucuronidase and lactic dehydrogenase. Percent cell loss approximates enzyme release indicating cell disruption at this shear stress. At a shear stress of 3 dynes/cm2, 3-glucuronidase release is greater than LDH release indicating that the PMNs are expelling granules into the extracellular fluid at this higher shear stress without concomitant cytoplasmic enzyme release. Pretreatment of PMNs with PGEi plus RA-233 or PGEi plus theophylline produces an approximately 25% reduction of cell loss and release of 3-glucuronidase and LDH release after exposure to a shear stress of 3 dynes/cm2. No significant effects of PGEi plus RA-233 are observed at 1 dynes/cm2. Pretreatment of PMNs with PGI2 plus RA-233 produces no reduction of PMN response to mechanical stimuli. PMNs incubated with dipyridamole and exposed to a shear stress of 3 dynes/cm2 show a significant reduction in cell loss, granule release, and lysis. The suppressive effect of dipyridamole appears to be additive with the effect of PGEi. Leukocytes pretreated with PGEi plus dipyridamole and exposed to shear stresses of 3 dynes/cm2 show a greater decrease of cell loss and enzyme release than pretreatment with dipyridamole alone or PGEi plus a phosphodiesterase inhibitor.
dc.format.digitalOriginreformatted digital
dc.format.extent94 pp
dc.identifier.callnoTHESIS CH.E. 1981 ROTHBERG
dc.identifier.citationRothberg, Jeanne Mays. "Effects of antiplatelet agents on polymorphonuclear leukocytes exposed to mechanical trauma." (1981) Master’s Thesis, Rice University. <a href="https://hdl.handle.net/1911/104166">https://hdl.handle.net/1911/104166</a>.
dc.identifier.digitalRICE1793
dc.identifier.urihttps://hdl.handle.net/1911/104166
dc.language.isoeng
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.titleEffects of antiplatelet agents on polymorphonuclear leukocytes exposed to mechanical trauma
dc.typeThesis
dc.type.materialText
thesis.degree.departmentChemical Engineering
thesis.degree.disciplineEngineering
thesis.degree.grantorRice University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science
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