The role of hyaluronan and interleukin 8 in the migration of chronic lymphocytic leukemia cells within lymphoreticular tissues.

摘要: Malignant lymphocyte migration into and within lymphoreticular tissue is an important aspect of chronic lymphocytic leukemia (CLL), yet little known about the processes involved. Our previous studies integrin expression function in CLL have shown that abnormal cells are relatively nonadhesive nonmotile on protein ligands these receptors. Here we show adhere to a non-protein ligand, hyaluronan (HA), become motile (as assessed by both Boyden chamber time-lapse video microscopy) this ligand when stimulated with interleukin (IL) 8. The combined presence HA IL-8 was essential for motility because did not stimulate movement other surfaces. Blocking antibodies showed mediated receptor HA-mediated (RHAMM), without involvement CD44. Moreover, confocal microscopy polarized distribution RHAMM F-actin, but CD44, which had IL-8. Immunohistochemical nodes spleen demonstrated abundant reticular network HA-containing fibers throughout diseased splenic white pulp. red pulp luminal surface high endothelial venules lacked HA. ubiquitously present tissues. were move spontaneously fibroblast monolayers derived from lymphoid tissue; largely blocked hyaluronidase or anti-RHAMM anti-IL-8 antibodies. These indicate IL-8-induced likely be cell through tissue.