Haegel-Kronenberger H, de la Salle H, Bohbot A, Oberling F, Cazenave J P, Hanau D
Institut National de la Santé et de la Recherche Médicale CJF 94-03, and INSERM Unité 311, Etablissement de Transfusion Sanguine de Strasbourg, France.
J Immunol. 1998 Oct 15;161(8):3902-11.
The regulation and function of the CD44 family of surface glycoproteins were investigated in human monocyte-derived dendritic cells (DCs). Variant CD44 isoform transcripts encoding exons v3, v6, and v9 are differently regulated during the differentiation of monocytes into DCs. TNF-alpha treatment, which induces the maturation of DCs, up-regulates the expression of all v3-, v6-, and v9-containing isoforms examined. CD44 molecules are involved in the adhesion of DCs to immobilized hyaluronate (HA), and v3- and v6-containing variants participate in this function, whereas anti-CD44v9 mAbs were unable to inhibit DC adhesion to HA. The consequences of ligand binding to CD44 were examined by culturing DCs on dishes coated with HA or various anti-CD44 mAbs. HA, the anti-pan CD44 mAb J173, and mAbs directed against v6- and v9-containing (but not v3-containing) isoforms provoked DC aggregation, phenotypic and functional maturation, and the secretion of IL-8, TNF-alpha, IL-1beta, and granulocyte-macrophage CSF. In addition, IL-6, IL-10, and IL-12 were released by DCs stimulated with either J173 or HA, although these cytokines were not detected or were found only at low levels in the culture supernatants of DCs treated with anti-CD44v6 or anti-CD44v9 mAbs. Our study points to distinct capacities of the v3-, v6-, and v9-containing isoforms expressed by human DCs to mediate cell adhesion to HA and/or a signal inducing DC maturation and the secretion of cytokines.
在人单核细胞衍生的树突状细胞（DCs）中研究了表面糖蛋白CD44家族的调控及功能。在单核细胞分化为DCs的过程中，编码外显子v3、v6和v9的可变CD44同种型转录本受到不同调控。诱导DCs成熟的肿瘤坏死因子-α（TNF-α）处理可上调所有检测到的含v3、v6和v9同种型的表达。CD44分子参与DCs与固定化透明质酸（HA）的黏附，含v3和v6的变体参与此功能，而抗CD44v9单克隆抗体无法抑制DCs与HA的黏附。通过在包被有HA或各种抗CD44单克隆抗体的培养皿上培养DCs来研究配体与CD44结合的后果。HA、抗泛CD44单克隆抗体J173以及针对含v6和v9（而非含v3）同种型的单克隆抗体可引发DCs聚集、表型和功能成熟以及IL-8、TNF-α、IL-1β和粒细胞-巨噬细胞集落刺激因子的分泌。此外，用J173或HA刺激的DCs可释放IL-6、IL-10和IL-12，尽管在用抗CD44v6或抗CD44v9单克隆抗体处理的DCs培养上清液中未检测到这些细胞因子或仅发现其水平较低。我们的研究指出，人DCs表达的含v3、v6和v9的同种型具有介导细胞与HA黏附及/或诱导DC成熟和细胞因子分泌信号的不同能力。
