Multistep navigation and the combinatorial control of leukocyte chemotaxis.
Multistep navigation and the combinatorial control of leukocyte chemotaxis.
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多步导航和白细胞趋化性的组合控制。
DOI：
10.1083/jcb.139.5.1349
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发表时间：
1997-12-01
影响因子：
7.8
通讯作者：
Butcher, E C
中科院分区：
文献类型：
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作者：
Foxman, E F;Campbell, J J;Butcher, E C
在组织内迁移的细胞可能会遇到复杂的空间和时间模式的多个化学吸引信号。为了了解白细胞在这样的设置中的导航，我们探索了中性粒细胞在模型场景中的迁移行为，在模型场景中，中性粒细胞被呈现为两种不同配置的化学源。我们证明，在广泛的条件下，中性粒细胞可以向下迁移局部的化学吸引剂梯度，以响应不同的化学吸引剂的远距离梯度。此外，细胞在沿初始梯度向上迁移到饱和的、无定向的初始诱导剂浓度后，可以有效地对次要的远距离激动剂进行化学趋化。总之，这些观察结果表明，在复杂的化学吸引剂领域中，细胞可能会从一个梯度逐步导航到另一个梯度。在模型系统中证实了这种顺序导航的重要性，在该模型系统中，中性粒细胞归巢到定义的区域(A)需要对以定义的空间阵列呈现的激动剂的系列反应，并且(B)是激动剂组合和遇到梯度的序列的函数。我们提出了一个趋化物质定向迁移的多步骤模型，该模型要求白细胞显示多个趋化物质受体才能成功归巢，并提供微环境定位的组合决定。
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.