|
|
|
|
|
|
|
||
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; and the Center for Molecular Biology and
Medicine, Foothill Research Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304
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.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
