The role of interleukin-8 and monocyte chemoattractant protein-1 in BCG vaccine induced resistance to Mycobacterium tuberculosis : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2002]
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| Subjects: |
| Abstract: | ABSTRACT: Alveolar macrophages harvested from BCG-vaccinated guinea pigs produced significantly more mRNA and protein for interleukin (IL)-8 than alveolar macrophages harvested from non-vaccinated guinea pigs at 12 and 24 hours post stimulation with LPS (10microg/ml) or infection with Mycobacterium tuberculosis H37Ra or H37Rv. Infection with attenuated M. tuberculosis (H37Ra) stimulated alveolar macrophages isolated from BCG-vaccinated guinea pigs to produce significantly more IL-8 mRNA when compared to alveolar macrophages infected with virulent strain (H37Rv) at 12 and 24 hours with heat-killed H37Ra, heat-killed H37Rv, and H37Rv cell, wall, but not mannose-capped lipoarabinomannan (ManLAM), when compared to cells stimulated with media alone. Neutrophils were harvested from the blood of non-vaccinated or M. bovis BCG-vaccinated guinea pigs and tested for their ability to migrate toward recombinant guinea pig (rgp)IL-8 in 96 well chemotactic chambers. Recombinant gpIL-8 induced significant chemotaxis in neutrophils from both non-vaccinated and BCG-vaccinated guinea pigs, with optimal chemotaxis occurring at a concentration of 10⁻⁷M. Cells pre-stimulated with rgpIL-8 then restimulated with LPS (10microg/ml) or infected in vitro with M. tuberculosis H37Ra (MOI 1:1) showed elevated levels of IL-8 and tumor necrosis factor (TNF)-[alpha] mRNA and protein as well as superoxide, but not mRNA for MCP-1, interferon (IFN)-γ, or transforming growth factor (TGF)-[beta] when compared to neutrophils pre-stimulated with media alone. Intradermal injections of rgpIL-8 into BCG-vaccinated guinea pigs produced notable skin reaction that could be significantly reduced by co-injection of anti-rgpIL-8 antibody. Histopathological scores of biopsied skin reactions showed marked polymorphonuclear leukocyte (PMN) infiltration associated with rgpIL-8 intradermal injection and only mild PMN infiltration with rgpIL-8 + anti-rgpIL-8 antibody. This entire study makes a case that IL-8 may have an important role to play in the early stages of the host defense against infections with Mycobacterium tuberculosis. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Graduate School of Biomedical Sciences of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy December 2002." Approved as to style and content by: David N. McMurrary, Roger Smith III, James E. Samuel, Vernon L. Tesh, John M. Quarles. |
| Physical Description: | xii, 77 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 67-76). |