Limits...
Multistep navigation and the combinatorial control of leukocyte chemotaxis.

Foxman EF, Campbell JJ, Butcher EC - J. Cell Biol. (1997)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Neutrophils can migrate in opposite directions in the  same field of overlapping chemoattractant gradients. The migratory behavior of neutrophils placed in IL-8 (originating in a well  below the picture) and LTB4 (originating in a well above the picture) was recorded by time-lapse video microscopy. The image  shows cells at the leading edge of each population 90 min after  the start of the assay, when each population is nearing a common  point between the starting wells. Arrows indicate the migration  paths of several representative cells over the next 15 min. Most  cells that started at the IL-8 source migrate towards the LTB4  source and vice versa; occasionally, a cell is observed to change  directions (i.e., cell indicated by *).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2140208&req=5

Figure 3: Neutrophils can migrate in opposite directions in the same field of overlapping chemoattractant gradients. The migratory behavior of neutrophils placed in IL-8 (originating in a well below the picture) and LTB4 (originating in a well above the picture) was recorded by time-lapse video microscopy. The image shows cells at the leading edge of each population 90 min after the start of the assay, when each population is nearing a common point between the starting wells. Arrows indicate the migration paths of several representative cells over the next 15 min. Most cells that started at the IL-8 source migrate towards the LTB4 source and vice versa; occasionally, a cell is observed to change directions (i.e., cell indicated by *).

Mentions: One prediction from these studies would be that, if neutrophils were placed with IL-8 in one well, and other neutrophils with LTB4 in another well 2.2 mm away, the cells should migrate in opposite directions with each cell population responding to the agonist in the distant well. Fig. 3 illustrates traces of neutrophils migrating from an IL-8 to an LTB4 source or (in the opposite direction) from the LTB4 source to the IL-8 source, over a 15-min period (105–120 min) as they approach a midpoint between the two source wells. The traces emphasize the striking, opposing directionality of chemotactic migration of the two populations as they come together.


Multistep navigation and the combinatorial control of leukocyte chemotaxis.

Foxman EF, Campbell JJ, Butcher EC - J. Cell Biol. (1997)

Neutrophils can migrate in opposite directions in the  same field of overlapping chemoattractant gradients. The migratory behavior of neutrophils placed in IL-8 (originating in a well  below the picture) and LTB4 (originating in a well above the picture) was recorded by time-lapse video microscopy. The image  shows cells at the leading edge of each population 90 min after  the start of the assay, when each population is nearing a common  point between the starting wells. Arrows indicate the migration  paths of several representative cells over the next 15 min. Most  cells that started at the IL-8 source migrate towards the LTB4  source and vice versa; occasionally, a cell is observed to change  directions (i.e., cell indicated by *).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2140208&req=5

Figure 3: Neutrophils can migrate in opposite directions in the same field of overlapping chemoattractant gradients. The migratory behavior of neutrophils placed in IL-8 (originating in a well below the picture) and LTB4 (originating in a well above the picture) was recorded by time-lapse video microscopy. The image shows cells at the leading edge of each population 90 min after the start of the assay, when each population is nearing a common point between the starting wells. Arrows indicate the migration paths of several representative cells over the next 15 min. Most cells that started at the IL-8 source migrate towards the LTB4 source and vice versa; occasionally, a cell is observed to change directions (i.e., cell indicated by *).
Mentions: One prediction from these studies would be that, if neutrophils were placed with IL-8 in one well, and other neutrophils with LTB4 in another well 2.2 mm away, the cells should migrate in opposite directions with each cell population responding to the agonist in the distant well. Fig. 3 illustrates traces of neutrophils migrating from an IL-8 to an LTB4 source or (in the opposite direction) from the LTB4 source to the IL-8 source, over a 15-min period (105–120 min) as they approach a midpoint between the two source wells. The traces emphasize the striking, opposing directionality of chemotactic migration of the two populations as they come together.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus