Labowsky M, Fahmy T M
Ansama Research, 5 Highview Ct., Wayne, NJ 07470: 973-831-8766:
Chem Eng Sci. 2012 May 28;74:114-123. doi: 10.1016/j.ces.2012.02.001. Epub 2012 Feb 6.
The diffusive transfer, or paracrine delivery, of chemical factors during the interaction of an emitting cell and a receiving cell is a ubiquitous cellular process that facilitates information exchange between the cells an/or to bystander cells. In the cellular immune response this exchange governs the magnitude and breadth of killing of cellular targets, inflammation or tolerance. Paracrine delivery is examined here by solving the the steady-state diffusion equation for the concentration field surrounding two intensely interacting, equi-sized cells on which surface kinetics limits the rates of factor emission and absorption. These chemical factors may be cytokines, such as Interlukins and Interferons, but the results are presented in a generic form so as to be applicable to any chemical factor and/or cell-type interaction. In addition to providing overall transfer rates and transfer efficiencies, the results also indicate that when the receiving cell is naïve, with few factor receptors on its surface, there may be a significant accumulation of factor in the synaptic region between the cells with a consequent release of factor to the medium where it can signal bystander cells. This factor accumulation may play a critical role in activating a naïve receiving cell. As the receiving cell activates and becomes more absorbent, the factor accumulation diminishes, as does potential bystander signaling.
在发射细胞与接收细胞相互作用期间,化学因子的扩散传递(即旁分泌传递)是一种普遍存在的细胞过程,它促进了细胞之间和/或与旁观者细胞之间的信息交换。在细胞免疫反应中,这种交换控制着细胞靶标的杀伤程度和广度、炎症或耐受性。本文通过求解围绕两个强烈相互作用的等大小细胞的浓度场的稳态扩散方程来研究旁分泌传递,在这两个细胞表面动力学限制了因子发射和吸收的速率。这些化学因子可能是细胞因子,如白细胞介素和干扰素,但结果以通用形式呈现,以便适用于任何化学因子和/或细胞类型的相互作用。除了提供总体传递速率和传递效率外,结果还表明,当接收细胞处于初始状态,其表面几乎没有因子受体时,细胞间突触区域可能会有大量因子积累,从而导致因子释放到培养基中,在那里它可以向旁观者细胞发出信号。这种因子积累可能在激活初始接收细胞中起关键作用。随着接收细胞激活并变得更具吸收性,因子积累减少,潜在的旁观者信号传递也减少。