Palmieri G, Gismondi A, Galandrini R, Milella M, Serra A, De Maria R, Santoni A
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Nat Immun. 1996;15(2-3):147-53.
NK cells are endowed with a wide array of adhesion molecules which mediate their interaction with endothelium and extracellular matrix components. We have shown that cross-linking of beta 1 integrins and CD44 on human NK cells induces a signal transduction pathway involving both tyrosine kinase activation and the modulation of intracellular calcium levels. Our studies have also demonstrated the ability of beta 1 integrins and CD44 to upregulate both the spontaneous and the CD16-triggered cytotoxic activity of human NK cells. Although the molecular mechanisms responsible for this costimulatory activity have not been defined yet, our studies indicate that the simultaneous cross-linking of beta 1 integrins and CD44 results in a synergistic effect on CD16-mediated enhancement of intracellular free calcium concentration, and suggest that this may be relevant for the cooperation observed.
自然杀伤细胞(NK细胞)具有多种粘附分子,这些分子介导它们与内皮细胞和细胞外基质成分的相互作用。我们已经表明,人NK细胞上β1整合素和CD44的交联可诱导一条信号转导途径,该途径涉及酪氨酸激酶激活和细胞内钙水平的调节。我们的研究还证明了β1整合素和CD44上调人NK细胞自发的以及CD16触发的细胞毒性活性的能力。尽管尚未确定负责这种共刺激活性的分子机制,但我们的研究表明,β1整合素和CD44的同时交联对CD16介导的细胞内游离钙浓度的增强产生协同作用,并表明这可能与所观察到的协同作用有关。