The role of leukocyte function-associated antigen-1 in animal models of inflammation
| Autor: | Stephen E. Fogal, Patricia L. Reilly, Nancy Haynes, Raymond J. Winquist, Gerald Nabozny, Sudha Desai, Maret Panzenbeck, Donald Souza |
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| Rok vydání: | 2001 |
| Předmět: |
Male
T cell Antigen presentation Inflammation Mice SCID Immunoglobulin E Imidazolidines Peripheral blood mononuclear cell Mice Antigen Mice Inbred NOD medicine Animals Humans Hypersensitivity Delayed Saimiri Pharmacology biology Imidazoles Lymphocyte Function-Associated Antigen-1 Hypersensitivity reaction Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Immunoglobulin G Immunology biology.protein Leukocytes Mononuclear Antibody medicine.symptom Immunosuppressive Agents |
| Zdroj: | European journal of pharmacology. 429(1-3) |
| ISSN: | 0014-2999 |
| Popis: | Both preclinical and clinical data have identified leukocyte function-associated antigen-1 (LFA-1) as an important component of inflammatory disease states. We evaluated small molecule inhibitors of this glycoprotein in several animal models in which the inflammatory process is dependent on human or non-human primate LFA-1. (R)-5(4-bromobenzyl)-3(3,5-dichlorophenyl)-1,5-dimethylimidazolidine-2,4-dione, BIRT 377, effectively suppressed the production of human immunoglobulin (IgG) following reconstitution of severe combined immunodeficient (SCID) mice with human peripheral blood mononuclear cells. The BIRT 377 analog, BIX 642, inhibited the cellular infiltrate and increase in skin thickness associated with the delayed-type hypersensitivity reaction in previously immunized squirrel monkeys challenged with antigen. BIX 642 also inhibited the trans-vivo delayed-type hypersensitivity response in the footpads of SCID mice injected with human peripheral blood mononuclear cells and donor-sensitive antigen. These results demonstrate the efficacy of small molecule inhibitors of LFA-1 in preclinical models of inflammation dependent on human or non-human primate LFA-1. |
| Databáze: | OpenAIRE |
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