1995 Fiscal Year Final Research Report Summary
THE ROLE OF LIPID A IN ENDOTOXIN-INDUCED UVEITIS
| Project/Area Number |
06671751
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | UNIVERSITY OF TOKYO |
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Principal Investigator |
FUJINO Yujiro M.D., University of Tokyo, Department of Ophthalmology, Assistant Professor, 医学部, 講師 (30143465)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Atsushi Ph.D., Senju Phamaceutical Co., LTD., Strategic Planning & Business Development,, 研究開発室, 研究員
TAKAHASHI Tadashi M.D., University of Tokyo, Department of Ophthalmology, Assistant, 医学部, 助手 (90197153)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Endotoxin-induced Uveitis / Lipopolysaccharide / Lipid A / Cytokine-induced Neutrophil Chemoattractant / Neutrophil |
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| Research Abstract |
Part I-Comparative clinical study of LPS and LA groups
The LPS and LA successfully induced uveitis and the peak of the ocular inflammation was obtained with 1000 mug/kg and 100 mug/kg, respectively. Cells in the AC were more numerous in the LA group than the LPS group at any given level of protein concentration.
Part II-Analysis of the CINC family in LPS and LA groups
The time course variation in the CINC family concentration in AH and serum samples obtained from both LPS and LA groups was assessed by EIA.The CINC-1 level in AH showed higher concentration in the LPS group compared to the LA group. The serum level of CINC-1 peaked at 6 hours in both groups and was also significantly higher in the LPS-group. The AH fromthe LPS group possessed stronger chemoattractant activity than the AH from the LA group. The evaluation of the cell infiltration into the AC in the rats injected with intravenous recombinant CINC-1 revealed that CINC-1 inhibited the migration of the inflammatory cells into the AC in a dose-dependent manner.
It has already been reported that CINC-1, when present at concentrations over 10 ng/mL,promotes the shedding of L-selectin from the neutrophil membrane, which disables the neutrophils to interact with vascular endothelium. Thus, the high level of CINC-1 in the intravascular compartment of the LPS model seemed to be a plausible altemative to explain the lower cell migration into the AC.The LA-induced uveitis induced more inflammation in the eye than did the LPS-induced uveitis, without altering excessively the systemic homeostasis. These findings should be considered for further selection of uveitis model.
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