Suzuki A, Andrew D P, Gonzalo J A, Fukumoto M, Spellberg J, Hashiyama M, Takimoto H, Gerwin N, Webb I, Molineux G, Amakawa R, Tada Y, Wakeham A, Brown J, McNiece I, Ley K, Butcher E C, Suda T, Gutierrez-Ramos J C, Mak T W
Amgen Institute, Ontario Cancer Institute, Department of Medical Biophysics, Toronto, Canada.
Blood. 1996 May 1;87(9):3550-62.
CD34 is expressed on the surface of hematopoietic stem/progenitor cells, stromal cells, and on the surface of high-endothelial venules (HEV). CD34 binds L-selectin, an adhesion molecule important for leukocyte rolling on venules and lymphocyte homing to peripheral lymph nodes (PLN). We generated CD34-deficient mutant animals through the use of homologous recombination. Wild-type and mutant animals showed no differences in lymphocyte binding to PLN HEV, in leukocyte rolling on venules or homing to PLN, in neutrophil extravasation into peritoneum in response to inflammatory stimulus, nor in delayed type hypersensitivity. Anti-L-selectin monoclonal antibody (MEL-14) also inhibited these immune responses similarly in both CD34-deficient and wild-type mice. However, eosinophil accumulation in the lung after inhalation of a model allergen, ovalbumin, is several-fold lower in mutant mice. We found no abnormalities in hematopoiesis in adult mice and interactions between mutant progenitor cells and a stromal cell line in vitro were normal. No differences existed in the recovery of progenitor cells after 5-fluorouracil treatment, nor in the mobilization of progenitor cells after granulocyte colony-stimulating factor treatment compared with wild-type animals. Surprisingly, although CD34 was not expressed in these mice, a portion of its 90-kD band crossreactive with MECA79 remained after Western blot. Thus, we have identified an additional molecule(s) that might be involved in leukocyte trafficking. These results indicate that CD34 plays an important role in eosinophil trafficking into the lung.
CD34在造血干/祖细胞、基质细胞以及高内皮微静脉（HEV）表面表达。CD34与L-选择素结合，L-选择素是一种对白细胞在微静脉上滚动以及淋巴细胞归巢至外周淋巴结（PLN）很重要的黏附分子。我们通过同源重组产生了CD34缺陷型突变动物。野生型和突变型动物在淋巴细胞与PLN的HEV结合、白细胞在微静脉上滚动或归巢至PLN、中性粒细胞在炎症刺激下向腹膜渗出以及迟发型超敏反应方面均无差异。抗L-选择素单克隆抗体（MEL-14）在CD34缺陷型和野生型小鼠中对这些免疫反应的抑制作用相似。然而，吸入模型变应原卵清蛋白后，突变型小鼠肺中嗜酸性粒细胞的积聚比野生型小鼠低几倍。我们发现成年小鼠的造血功能无异常，且突变型祖细胞与体外基质细胞系之间的相互作用正常。与野生型动物相比，5-氟尿嘧啶处理后祖细胞的恢复以及粒细胞集落刺激因子处理后祖细胞的动员均无差异。令人惊讶的是，尽管这些小鼠中不表达CD34，但蛋白质印迹后仍保留了一部分与MECA79交叉反应的90-kD条带。因此，我们鉴定出了一种可能参与白细胞转运的其他分子。这些结果表明，CD34在嗜酸性粒细胞向肺内的转运中起重要作用。
