P274	Lymphatic microvessel endothelial cells exposed to inflammatory stimuli change pattern of chemokine expression and leukocyte recruitment.
E.Vecile, R.Cattaruzzi, F.Petrera, E.Gustini, O.Burrone, G.Stanta, A.Dobrina
Department of Physiology and Pathology, University of Trieste, Trieste, IT.

Chemokine production by blood vessel endothelial cells is well documented. In contrast, there is only limited information regarding the expression of chemokines by the lymphatic endothelium. We have previously developed an experimental protocol for the induction of a lymphatic vessel endothelium hyperplasia in the peritoneum of mice (Exp. Cell Res., 246: 368-375, 1999). This model system was used to investigate the profile of chemokine expression in murine lymphatic endothelial primary cultures in the presence or absence of interleukin-1 (IL-1), gamma interferon (γI), or gram negative bacteria endotoxin (LPS). A functional chemotactic assay on purified populations of murine PMN, lymphocytes, macrophages and dendritic cells using culture supernatants from these endothelial cells evidenced significant changes of leukocyte chemotaxis after exposure of leukocytes and/or lymphatic endothelial cells to inflammatory stimuli. Inhibition experiments using blocking moAbs directed against CXC, CC, and C type chemokines evidenced a variable role of specific chemokines in leukocyte chemotaxis in the different conditions. Consistent with these observations was the expression of the apparently most involved chemokines C10, JE, SLC, MIG and MIP-2, as studied by quantitative PCR analysis on total lymphatic endothelial cell RNA before and after exposure of the cells to cytokines or LPS. Finally, RNA interference experiments with iRNA to chemokine receptors CCR1, CCR2 and CCR3, enabled us to state the specific role of each of these receptors in the in vivo recruitment into lymphatic vessels of various mononuclear leukocyte cell lines, including dendritic cells. These studies provide new indications about the signals leading leukocyte recirculation within the lymphatic system.

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