Degree Type

Dissertation

Date of Award

1994

Degree Name

Doctor of Philosophy

Department

Veterinary Pathology

First Advisor

Margaret L. Harbison

Second Advisor

John P. Kluge

Abstract

E-selectin, an endothelial cell adhesion molecule, is expressed on the surface of activated endothelial cells. Its role in neutrophil recruitment in acute murine inflammation, a previously undescribed entity, was the focus of this work. The interaction between P-selectin and E-selectin in neutrophil extravasation was also investigated;Two murine models of acute inflammation were utilized in this work: acute pneumonitis induced by intranasal (IN) instillation of bacterial lipopolysaccharide (LPS) and chemical peritonitis induced by intraperitoneal (IP) injection of thioglycollate broth. Intranasal LPS, a novel model, resulted in a progressive influx of neutrophils into the lungs beginning near airways and extending into distant alveoli 4-6 hours later. Intraperitoneal thioglycollate is a model commonly used to examine the role of adhesion molecules in acute inflammation;E-selectin expression, which peaked 4-6 hours post-treatment, was immunohistochemically detected on the endothelium of scattered vessels in the lungs of mice following IN instillation of LPS. P-selectin was detected in endothelial cells in control mouse lungs and increased post-treatment with IN LPS;Blocking with anti-E-selectin MAb did not decrease the neutrophil count in the peritoneal cavity following IP injection of thioglycollate. Nor did these antibodies decrease the neutrophil count in the bronchoalveolar lavage of mice 2 hours after IN instillation of LPS; whereas, by 6 hours post-treatment, there was a moderate decrease. However, when anti-P-selectin MAb were combined with the anti-E-selectin MAb, a significant increase in blocking was seen in the 6 hour group, demonstrating a redundancy in the function of these molecules. A carbohydrate analog of the selectin ligand was unable to block neutrophil influx in either model;Transgenic mice deficient in the gene for E-selectin had no macro- or microscopic abnormalities when compared to wild-type mice. They did have slightly elevated numbers of neutrophils in circulating in blood. However, neutrophil numbers in the peritoneal lavage of E-selectin deficient mice were not different from wild-type mice after IP thioglycollate. In conclusion, the role of E-selectin in acute murine inflammation is one which overlaps with P-selectin.

DOI

https://doi.org/10.31274/rtd-180813-9824

Publisher

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

Copyright Owner

Polly Ann Knaack

Language

en

Proquest ID

AAI9424235

File Format

application/pdf

File Size

138 pages

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