Abstracts (complete list) - Wissenschaft Online

David Frommhold, Andreas Ludwig, M. Gabi Bixel, Alexander Zarbock, Annette G.
Beck-Sickinger, Alma Zernecke, Christian Weber, Dietmar Vestweber, Klaus Ley, Markus
Sperandio
Sialyltransferase ST3Gal-IV interferes with chemokinedependent
leukocyte adhesion during inflammation
Recent in-vitro findings have demonstrated a role of sialylation for chemokine receptor
binding to its ligand. This prompted us to investigate chemokine-induced leukocyte
adhesion in inflamed post-capillary cremaster muscle venules of α2,3 sialyltransferase
(ST3Gal-IV)-deficient mice. We found a marked reduction of leukocyte adhesion in
unstimulated cremaster muscle venules upon injection of keratinocyte-derived
chemokine (KC), which interacts with chemokine receptor CXCR2. In TNF-α-treated
cremaster muscle venules where leukocyte adhesion depends on the overlapping
function of CXCR2 and E-selectin, leukocyte adhesion was significantly decreased in
ST3Gal-IV-/- mice in those experiments where E-selectin function was blocked.
Additional in vitro assays revealed that KC-binding to CXCR-2 on isolated ST3Gal-IV-/-
neutrophils was markedly reduced. Furthermore, KC-mediated adhesion of ST3Gal-IV-/-
leukocytes at physiological flow conditions was significantly reduced as well as
transendothelial migration of ST3Gal-IV-/- leukocytes in response to KC. In human
neutrophils, enzymatic desialylation led to decreased binding of CXCR-2 ligands to
CXCR-2 and diminished neutrophil degranulation in response to these chemokines.
Taken together, our results provide substantial evidence that sialylation by ST3Gal-IV
significantly contributes to CXCR2-mediated leukocyte functions and is required for
leukocyte arrest and extravasation during inflammation in vivo.