Stoop Reinout, Gál István, Glant Tibor T, McNeish John D, Mikecz Katalin
Section of Biochemistry and Molecular Biology, Department of Orthopedic Surgery, Rush University at Rush-Presbyterian-St. Luke's Medical Center, Chicago 60612, USA.
Eur J Immunol. 2002 Sep;32(9):2532-42. doi: 10.1002/1521-4141(200209)32:9<2532::AID-IMMU2532>3.0.CO;2-A.
CD44 has been implicated in hyaluronan (HA)-dependent primary adhesion between leukocytes and endothelium. We studied the trafficking of lymphocytes of CD44-deficient DBA/1 mice under normal conditions, and during chronic and transient forms of inflammation. Animals homozygous for the CD44 mutation (CD44(-/-)) showed no abnormalities in the composition of the lympho-hemopoietic system, but their leukocytes could not recognize HA as an adhesion ligand. T cells from CD44-deficient mice responded normally to immunization with type II collagen or stimulation with a bacterial superantigen. Lymphocytes harvested from naive CD44(-/-) and wild-type (WT) animals showed similar trafficking properties when injected into naive recipients. However, cells from WT and CD44-deficient mice with collagen-induced arthritis showed distinct migration kinetics upon transfer to arthritic recipients. While lymphocytes from CD44(-/-) mice preferentially homed to lymph nodes, their entry into the inflamed synovial joints was delayed as compared with WT cells. Similar differences were observed in the migration kinetics of CD44-deficient and CD44-competent (CD44(+/+)) lymphocytes in bacterial superantigen-induced peritonitis. These results suggest that CD44 plays opposite roles in the regulation of leukocyte traffic to inflammatory sites versus the lymph nodes. CD44-deficient lymphocytes from animals with chronic arthritis, but not from those with transient peritonitis, expressed markedly reduced levels of the lymph node homing receptor, L-selectin. Extreme down-modulation of L-selectin from CD44(-/-) cells in arthritic condition might be a counter-regulatory response, which, by extending lymphocyte transit time in the circulation at the expense of lymph node homing, allows CD44-deficient cells to gain entry to the site of chronic inflammation via secondary adhesion mechanisms.
CD44与透明质酸（HA）依赖的白细胞与内皮细胞之间的初始黏附有关。我们研究了正常条件下以及慢性和短暂性炎症期间CD44缺陷型DBA/1小鼠淋巴细胞的迁移情况。CD44突变纯合子动物（CD44(-/-)）的淋巴细胞造血系统组成无异常，但其白细胞无法将HA识别为黏附配体。来自CD44缺陷小鼠的T细胞对II型胶原免疫或细菌超抗原刺激反应正常。将来自未免疫的CD44(-/-)和野生型（WT）动物的淋巴细胞注射到未免疫的受体中时，它们表现出相似的迁移特性。然而，将患有胶原诱导性关节炎的WT和CD44缺陷小鼠的细胞转移到关节炎受体中时，它们表现出不同的迁移动力学。虽然来自CD44(-/-)小鼠的淋巴细胞优先归巢到淋巴结，但与WT细胞相比，它们进入炎症性滑膜关节的时间延迟。在细菌超抗原诱导的腹膜炎中，CD44缺陷和有CD44功能（CD44(+/+)）的淋巴细胞的迁移动力学也观察到类似差异。这些结果表明，CD44在调节白细胞向炎症部位与淋巴结的迁移中发挥相反作用。患有慢性关节炎动物的CD44缺陷淋巴细胞，但不包括患有短暂性腹膜炎动物的CD44缺陷淋巴细胞，其淋巴结归巢受体L-选择素的表达水平明显降低。在关节炎状态下，CD44(-/-)细胞中L-选择素的极端下调可能是一种反调节反应，即以牺牲淋巴结归巢为代价延长淋巴细胞在循环中的转运时间，使CD44缺陷细胞能够通过二级黏附机制进入慢性炎症部位。
