Mikecz K, Brennan F R, Kim J H, Glant T T
Department of Orthopedic Surgery, Rush Medical College at Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Nat Med. 1995 Jun;1(6):558-63. doi: 10.1038/nm0695-558.
A ubiquitous cell adhesion receptor, CD44, preferentially binds hyaluronan, a polysaccharide macromolecule that is present in most extracellular matrices. Hyaluronan molecules have large hydrodynamic volumes that entrap substantial amounts of water and can therefore control tissue hydration (swelling). CD44 is overexpressed by synovial cells and leukocytes, and hyaluronan is overproduced in the rheumatoid synovium and in other inflammatory sites. Nevertheless, the role of the CD44-hyaluronan interaction during inflammation is unclear. Our evidence shows that the CD44 receptor plays a critical role in governing the migration of inflammatory leukocytes into the extravascular compartment of the synovium in murine arthritis. An anti-CD44 antibody induces a rapid loss of CD44 from both leukocytes and synovial cells and displays an inhibitory effect on cell-extracellular matrix interactions in the synovium. As a result, the administration of such an antibody abrogates tissue swelling and leukocyte infiltration, two major components of inflammation.
一种广泛存在的细胞黏附受体CD44，优先结合透明质酸，透明质酸是一种存在于大多数细胞外基质中的多糖大分子。透明质酸分子具有较大的流体动力学体积，能截留大量水分，因此可以控制组织水合作用（肿胀）。滑膜细胞和白细胞中CD44表达上调，类风湿性滑膜和其他炎症部位透明质酸过度产生。然而，炎症过程中CD44-透明质酸相互作用的作用尚不清楚。我们的证据表明，CD44受体在控制炎症性白细胞迁移到小鼠关节炎滑膜血管外间隙中起关键作用。抗CD44抗体可导致白细胞和滑膜细胞表面的CD44迅速丢失，并对滑膜中的细胞-细胞外基质相互作用产生抑制作用。因此，给予这种抗体可消除组织肿胀和白细胞浸润，这是炎症的两个主要组成部分。
