Neutrophil adhesion and complement activation in the functioning myocardium.
dc.contributor.author | Kilgore, Kenneth Stanley | en_US |
dc.contributor.advisor | Lucchesi, Benedict R. | en_US |
dc.date.accessioned | 2014-02-24T16:18:27Z | |
dc.date.available | 2014-02-24T16:18:27Z | |
dc.date.issued | 1994 | en_US |
dc.identifier.other | (UMI)AAI9423230 | en_US |
dc.identifier.uri | http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9423230 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/103975 | |
dc.description.abstract | It has become evident that a number of factors are involved in the cellular alterations associated with myocardial ischemia/reperfusion injury. The inflammatory system, via complement activation and accumulation of neutrophils at the site of injury, has been associated with the extension of irreversible cell injury. The observation that inhibiting complement activation results in a decrease in neutrophil accumulation within the myocardium suggests that the complement system plays a significant role in neutrophil adherence. To investigate the role of complement in mediating neutrophil accumulation within the myocardium, experiments were conducted using the rabbit isolated heart perfused with human plasma and neutrophils. This model was utilized to test the hypothesis that activation of complement leads to the specific adhesion of neutrophils within the myocardium. Furthermore, this study attempted to discern the mechanism by which complement increases neutrophil adhesion and to determine the specific molecules involved in the adhesion of neutrophils. The effects of neutrophil adhesion on tissue damage and the mechanism of this injury also were examined. Activation of plasma complement components by the rabbit isolated heart was found to increase the accumulation of human neutrophils in the myocardium. Formation of the membrane attack complex and subsequent cell damage is necessary for the increase in neutrophil accumulation. In addition, a number of adhesion molecules including P-selectin and the CD11b/CD18 complex were found to be important in mediating the adhesion. Activation of neutrophils was confirmed by the presence of the neutrophil specific enzyme myeloperoxidase and the generation of oxygen-derived free radicals in the pulmonary effluent of hearts perfused with plasma and neutrophils. This neutrophil activation was found to result in an increase in the degree of myocardial damage as assessed by the use of a radiolabeled antibody specific for cardiac myosin. The results of this study indicate that activation of complement promotes adhesion of neutrophils within the myocardium, mediated by a number of cellular adhesion molecules. Furthermore, the increase in neutrophil adhesion resulted in enhanced damage to the myocardium. Thus, complement activation may indirectly extend the degree of damage following an acute ischemic event by promoting an increase in neutrophil accumulation. | en_US |
dc.format.extent | 123 p. | en_US |
dc.subject | Health Sciences, Pharmacology | en_US |
dc.subject | Health Sciences, Pathology | en_US |
dc.title | Neutrophil adhesion and complement activation in the functioning myocardium. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Pharmacology | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/103975/1/9423230.pdf | |
dc.description.filedescription | Description of 9423230.pdf : Restricted to UM users only. | en_US |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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