This study is directed towards characterizing the change in resistance of murine eyes to Pseudomonas aeruginosa bacterial infection altered by age and genetic background. Biochemical purification of bacterial pili and flagellar proteins, production of monoclonal (MAbs) and polyclonal antibodies to these proteins and immunization with the proteins and immunotherapy with MAbs or polyclonal antisera will be done in the in vivo mouse models of infection. Immunocytochemical, immunological and microbiological techniques will be employed to localize and determine the role of major histocompatibility (MHC) Class I and Class II antigens, T cell subsets, B cells, antibody and several glycoproteins and glycolipids (GMl gangliosides) and type IV collagen in infection. Lectin histochemistry and cytochemistry will be employed in vivo (eye and lacrimal gland) using immunofluorescence of routinely embedded 1 um sections as well as transmission electron microscopy and postembedding procedures with plastic etching and/or embedding in hydrophilic resins to determine ocular in situ biochemistry and lectins will be similarly employed in traditional biochemical assay procedures. Human post mortem autopsy corneas and mouse organ culture in vitro systems will be employed for adherence assay testing using scanning electron microscopy and quantitative microbiological procedures and these data related to and compared with information gained from the in vivo models. Bacterial surface components (glycocalyx) will be determined with lectin histochemistry, cytochemistry and biochemistry and additional inhibitory agents will be examined to further clarify the receptor/adhesin interaction between bacteria and host ocular tissue. The studies proposed will be of value in the development of immunotherapeutics and/or receptor analogs which either alone, or in concert, will serve to prevent or lessen bacterial infectivity and subsequent corneal inflammatory disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002986-12
Application #
3257295
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1979-04-01
Project End
1994-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
12
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
McClellan, Sharon A; Ekanayaka, Sandamali A; Li, Cui et al. (2015) Thrombomodulin Protects Against Bacterial Keratitis, Is Anti-Inflammatory, but Not Angiogenic. Invest Ophthalmol Vis Sci 56:8091-100
McClellan, Sharon; Jiang, Xiaoyu; Barrett, Ronald et al. (2015) High-mobility group box 1: a novel target for treatment of Pseudomonas aeruginosa keratitis. J Immunol 194:1776-87
Jiang, Xiaoyu; McClellan, Sharon A; Barrett, Ronald et al. (2014) HGF signaling impacts severity of Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci 55:2180-90
Li, Cui; McClellan, Sharon A; Barrett, Ronald et al. (2014) Interleukin 17 regulates Mer tyrosine kinase-positive cells in Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci 55:6886-900
Hazlett, Linda D; Jiang, Xiaoyu; McClellan, Sharon A (2014) IL-10 function, regulation, and in bacterial keratitis. J Ocul Pharmacol Ther 30:373-80
Foldenauer, Megan E B; McClellan, Sharon A; Berger, Elizabeth A et al. (2013) Mammalian target of rapamycin regulates IL-10 and resistance to Pseudomonas aeruginosa corneal infection. J Immunol 190:5649-58
Berger, Elizabeth A; McClellan, Sharon A; Vistisen, Kerry S et al. (2013) HIF-1? is essential for effective PMN bacterial killing, antimicrobial peptide production and apoptosis in Pseudomonas aeruginosa keratitis. PLoS Pathog 9:e1003457
Berger, Elizabeth A; Vistisen, Kerry S; Barrett, Ronald P et al. (2012) Effects of VIP on corneal reconstitution and homeostasis following Pseudomonas aeruginosa induced keratitis. Invest Ophthalmol Vis Sci 53:7432-9
Jiang, Xiaoyu; McClellan, Sharon A; Barrett, Ronald P et al. (2012) The role of VIP in cornea. Invest Ophthalmol Vis Sci 53:7560-6
Foldenauer, Megan E B; McClellan, Sharon A; Barrett, Ronald P et al. (2012) Substance P affects growth factors in Pseudomonas aeruginosa-infected mouse cornea. Cornea 31:1176-88

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