Cd44-Hyaluronic Acid Interactions in Il-2 Induced Vascular Leak Syndrome

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dc.contributor.authorMustafa, Amjaden
dc.contributor.committeechairNagarkatti, Prakash S.en
dc.contributor.committeecochairNagarkatti, Mitzien
dc.contributor.committeememberPopham, David L.en
dc.contributor.committeememberDuncan, Robert B. Jr.en
dc.contributor.departmentBiologyen
dc.date.accessioned2014-03-14T20:40:51Zen
dc.date.adate2001-07-02en
dc.date.available2014-03-14T20:40:51Zen
dc.date.issued2001-06-15en
dc.date.rdate2002-07-02en
dc.date.sdate2001-06-30en
dc.description.abstractImmunotherapy with IL-2 is accompanied by severe toxicity leading to development of vascular leak syndrome (VLS). Previous studies from our laboratory demonstrated that CD44 knockout mice exhibit marked decrease in IL-2 induced VLS, thereby suggesting a role for CD44 in VLS. In the current study we tested whether use of mAbs against CD44 or hyaluronic acid (HA), the ligand for CD44, can abrogate IL-2 induced VLS. Administration of IL-2 (75,000 U/mouse, three times a day for 4 days) into C57BL/6 mice triggered significant VLS in the lungs and liver. Interestingly, HA caused a marked increase in IL-2-induced VLS in the lungs and liver. In contrast, use of anti-CD44 mAbs reduced IL-2-induced VLS in the lungs and liver. The change in VLS seen following HA or anti-CD44 mAbs treatment was not due to any defect in lymphocyte migration or homing to various organs because histopathological studies in these mice demonstrated significant and often greater perivascular infiltration of lymphocytes when compared to mice treated with IL-2 alone. However, HA treatment exhibited a marked increase in IL-2-induced lymphokine-activated killer (LAK) cell activity while anti-CD44 mAbs treatment led to a significant decrease in IL-2-induced LAK cell activity. These studies demonstrate that HA or anti CD44 mAbs may serve as a useful tool to selectively alter the LAK activity as well as to prevent the toxicity induced by IL-2. Altering CD44-HA interactions in vivo may offer a novel therapeutic approach to prevent endothelial cell injury by cytotoxic lymphocytes in a variety of clinical diseases.en
dc.description.degreeMaster of Scienceen
dc.identifier.otheretd-06302001-001618en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-06302001-001618/en
dc.identifier.urihttp://hdl.handle.net/10919/33821en
dc.language.isoenen
dc.publisherVirginia Techen
dc.relation.haspartMasterETD.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectVascular Leak Syndromeen
dc.subjectCD44en
dc.subjectHyaluronateen
dc.titleCd44-Hyaluronic Acid Interactions in Il-2 Induced Vascular Leak Syndromeen
dc.typeThesisen
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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