Prior studies in our laboratory have demonstrated that passive transfer of low dose monoclonal antibody to viral glycoproteins given after HSV-1 corneal infection can prevent the establishment of permanent blinding corneal inflammation. How antibody exerts its protective effect is not known. However, since no protection was seen when virus neutralizing F(ab)2, fragments were given in place of intact antibody Fc gamma receptors (FcgammaRs) were though to be involved. Recent advances have led to a fundamental revision of the significance of FcgammaRs. Two types are now recognized - those that when ligated activate cells and those which inhibit cell activation. Where both types are expressed by the same cell the net cellular response triggered by co-ligation is thought to depend on the ratio of expression of the two opposing signals. We will use wildtype and FcgR gene knockout mice to test the premise that viral antigen:antibody complexes via co-ligation favor negative FcgR signaling, and so suppress herpes stromal keratitis development. Our studies will provide new information on the expression and function of FcgammaRs in ocular tissue and may lead to novel strategies for controlling corneal inflammation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011493-09
Application #
6927880
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Shen, Grace L
Project Start
1996-08-01
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2007-07-31
Support Year
9
Fiscal Year
2005
Total Cost
$292,000
Indirect Cost
Name
University of South Alabama
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
172750234
City
Mobile
State
AL
Country
United States
Zip Code
36688
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Fenton, Robin R; Molesworth-Kenyon, Sara; Oakes, John E et al. (2002) Linkage of IL-6 with neutrophil chemoattractant expression in virus-induced ocular inflammation. Invest Ophthalmol Vis Sci 43:737-43
Yan, X T; Zhuang, M; Oakes, J E et al. (2001) Autocrine action of IL-10 suppresses proinflammatory mediators and inflammation in the HSV-1-infected cornea. J Leukoc Biol 69:149-57
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Tumpey, T M; Cheng, H; Cook, D N et al. (1998) Absence of macrophage inflammatory protein-1alpha prevents the development of blinding herpes stromal keratitis. J Virol 72:3705-10
Tumpey, T M; Cheng, H; Yan, X T et al. (1998) Chemokine synthesis in the HSV-1-infected cornea and its suppression by interleukin-10. J Leukoc Biol 63:486-92