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

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.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Biology

Department dc:contributor.department

Biology

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2001

Author dc:creator

• Mustafa, Amjad

Chairs dc:contributor.committeechair

• Nagarkatti, Prakash S.
• Nagarkatti, Mitzi

Committee members dc:contributor.committeemember

• Popham, David L.
• Duncan, Robert B. Jr.

• Vascular Leak Syndrome
• CD44
• Hyaluronate

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

etd-06302001-001618

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/33821