Title page for ETD etd-06302001-001618

Type of Document Master's Thesis
Author Mustafa, Amjad
URN etd-06302001-001618
Title Cd44-Hyaluronic Acid Interactions in Il-2 Induced Vascular Leak Syndrome
Degree Master of Science
Department Biology
Advisory Committee
Advisor Name Title
Nagarkatti, Prakash S. Committee Chair
Nagarkatti, Mitzi Committee Co-Chair
Duncan, Robert B. Jr. Committee Member
Popham, David L. Committee Member
  • Vascular Leak Syndrome
  • CD44
  • Hyaluronate
Date of Defense 2001-06-15
Availability unrestricted
Immunotherapy 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.
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