Foxman E F, Campbell J J, Butcher E C
Laboratory of Immunology and Vascular Biology, Department of Pathology, and the Digestive Disease Center, Department of Medicine, Stanford University Medical School, Stanford, California 94305-5324, USA.
J Cell Biol. 1997 Dec 1;139(5):1349-60. doi: 10.1083/jcb.139.5.1349.
Cells migrating within tissues may encounter multiple chemoattractant signals in complex spatial and temporal patterns. To understand leukocyte navigation in such settings, we have explored the migratory behavior of neutrophils in model scenarios where they are presented with two chemoattractant sources in various configurations. We show that, over a wide range of conditions, neutrophils can migrate "down" a local chemoattractant gradient in response to a distant gradient of a different chemoattractant. Furthermore, cells can chemotax effectively to a secondary distant agonist after migrating up a primary gradient into a saturating, nonorienting concentration of an initial attractant. Together, these observations suggest the potential for cells' step-by-step navigation from one gradient to another in complex chemoattractant fields. The importance of such sequential navigation is confirmed here in a model system in which neutrophil homing to a defined domain (a) requires serial responses to agonists presented in a defined spatial array, and (b) is a function of both the agonist combination and the sequence in which gradients are encountered. We propose a multistep model of chemoattractant-directed migration, which requires that leukocytes display multiple chemoattractant receptors for successful homing and provides for combinatorial determination of microenvironmental localization.
在组织中迁移的细胞可能会以复杂的空间和时间模式遇到多种趋化因子信号。为了理解白细胞在这种情况下的导航机制，我们研究了中性粒细胞在模型场景中的迁移行为，在这些场景中，它们会面对以各种配置呈现的两种趋化因子来源。我们发现，在广泛的条件下，中性粒细胞可以响应不同趋化因子的远距离梯度，沿着局部趋化因子梯度“向下”迁移。此外，细胞在沿着初级梯度向上迁移到初始吸引剂的饱和、无定向浓度后，能够有效地向次级远距离激动剂进行趋化运动。这些观察结果共同表明，细胞在复杂的趋化因子场中从一个梯度逐步导航到另一个梯度具有潜在可能性。在一个模型系统中证实了这种顺序导航的重要性，在该系统中，中性粒细胞归巢到一个定义的区域：(a) 需要对以定义的空间阵列呈现的激动剂进行连续反应；(b) 是激动剂组合以及遇到梯度的顺序的函数。我们提出了一个趋化因子导向迁移的多步骤模型，该模型要求白细胞展示多种趋化因子受体以实现成功归巢，并为微环境定位的组合确定提供依据。
