부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cyto.2005.10.006 Byline: Eric Assier (a), Valerie Jullien (a), Jean Lefort (a), Jean-Louis Moreau (b), B. Boris Vargaftig (a), Jose Lapa e Silva J.R (c), Jacques Theze (b) Abbreviations: AUC, area under the curve; BALF, bronchoalveolar lavage fluid; MPO, myeloperoxidase activity; PMN, polymorphonuclear neutrophils; VLS, vascular leak syndrome Abstract: IL-2-induced vascular leak syndrome (VLS) is an important mechanism explaining the toxic effects of this cytokine and limiting its therapeutic use. We previously characterized a mouse model of IL-2-induced pulmonary VLS used to demonstrate that NK lymphocytes are involved in early/acute phase VLS (after one IL-2 injection). We also showed that NK cells and polymorphonuclear neutrophils (PMN) are involved in the late/chronic phase of the syndrome (after four daily IL-2 injections). In this study we use our mouse model to evaluate the role played by the IL-2 receptor (IL-2R) in VLS induction. Mouse and human IL-2R are different since the mouse IL-2Rbeta chain does not recognize IL-2. Here, we compare the acute and late VLS responses in human IL-2Rbeta transgenic and C57BL/6 wild type mice. Parameters linked to early phase VLS (bronchoconstriction and PMN mobilization) are enhanced in human IL-2Rbeta transgenic mice. By contrast, parameters used to measure late events (protein leakage and edema) are similar in human IL-2Rbeta transgenic mice and C57BL/6 wild type animals. However, after four IL-2 injections, the cellular content of the bronchoalveolar lavage fluids was different between the two types of animals. This study also characterizes a humanized animal model that could be further used to study human IL-2 activity and side effects in vivo. Author Affiliation: (a) Unite de Pharmacologie Cellulaire, Institut Pasteur, Paris, France (b) Unite d'Immuno-Genetique Cellulaire, Departement de Medecine Moleculaire, Institut Pasteur 25, Rue du Dr Roux 75724 Paris Cedex 15, France (c) Division of Pulmonary Medicine, Hospital Universitario Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Article History: Received 19 July 2005; Revised 21 October 2005; Accepted 28 October 2005