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Hookworm E/S products and host immune evasion and Cyclophilin-CD147 interactions in inflammation. Stephanie Constant / MITM Assistant Professor Dept. of Microbiology, Immunology and Tropical Medicine mtmslc@gwumc.edu 994-1138. 200. 116. 97. 80. 66. 55. 45. 30. 21. 14.
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Hookworm E/S products and host immune evasion and Cyclophilin-CD147 interactions in inflammation Stephanie Constant / MITM Assistant Professor Dept. of Microbiology, Immunology and Tropical Medicine mtmslc@gwumc.edu 994-1138
200 116 97 80 66 55 45 30 21 14 Na Ac Stephanie Constant / MITM PROJECT 1 Hookworm E/S products and host immune evasion Hsieh et al. 2004 J. Immunol. 173:2699 Loukas et al. 2005 FEMS 43:115 Funding: R01 AI-059280-01
Patients with active hookworm infection do not bind ES products ES products augment IFN-g production by >30 fold in human NK cells ES products bind only to NK cells 1,500 75 1,000 50 % bioES+ NK cells IFN-g (pg/ml) 500 25 0 0 +IL2 +IL12 +ES +IL2 +IL12 +ES Egg-negative (USA) Egg-negative (Brazil) Egg-positive (Brazil) ES binding Patient Category Stephanie Constant / MITM PROJECT 1 Hookworm E/S products and host immune evasion
7 5 6 4 5 Chemotactic index 3 4 Chemotactic index 3 2 *** 2 1 1 0 0 0 50 100 500 FMLP CyPA +isotype Medium CyPA CyPA +aCD147 CyPA (ng/ml) Stephanie Constant / MITM PROJECT 2 Cyclophilin-CD147 interactions in inflammation Extracellular cyclophilins induce leukocyte chemotaxis Cyclophilin-mediated chemotaxis is dependent on CD147 signaling Arora et al. 2005 J. Immunol. 175:517 Yurchenko et al. 2005 Immunology 117:301 Funding: R01 AI-067254-01
Mouse model of rheumatoid arthritis Mouse model of allergic asthma 10 2.5 9 isotype control 8 anti-CD147 7 2.0 isotype baseline 6 Clinical score anti-CD147 5 1.5 * 4 Ratio Penh ** ** 3 * 1.0 2 ** 1 0.5 0 21 23 27 30 34 37 41 44 48 51 55 58 Days 0 3.125 6.25 12.5 25 50 Methacholine (mg/ml) Stephanie Constant / MITM PROJECT 2 Cyclophilin-CD147 interactions in inflammation Gwinn et al. 2006 J. Immunol. 177:4870