'Reverse gear' cellular movement mediated by chemokines.

Abstract:

:We sought to model the mechanism by which leucocytes may be actively repulsed by a beta-chemokine signal. This model is used to interpret an apparent paradox in chemokine biology, whereby high levels of a T-cell chemoattractant, stromal cell derived factor-1 (SDF-1), are present in bone marrow and thymic tissues despite a paucity of mature T lymphocytes in these areas. We postulate the differential involvement in cell migration of the two binding sites on SDF-1 for its sole receptor, CXCR4, depending on whether high or low concentrations of SDF-1 are encountered by the cell. Site choice would be mediated by divergent affinities of the two binding interactions. We also propose differential signalling following SDF-1/CXCR4 interactions on the plasma membrane versus ligand/receptor complexes in endocytic vesicles. Preliminary data showing divergent susceptibility to kinase inhibitors depending on whether a cell is attracted to or repulsed by SDF-1, are consistent with this model. In terms of physical movement toward or away from a chemokine gradient, we compare the cycling of surface receptors during migration to the caterpillar drive of a tractor, which can change direction simply by altering the direction of rotation of its threads. Finally, the potential clinical implications of concentration-dependent, chemokine-based cell attraction and repulsion are discussed.

journal_name

Immunol Cell Biol

authors

Zlatopolskiy A,Laurence J

doi

10.1046/j.1440-1711.2001.01015.x

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

340-4

issue

4

eissn

0818-9641

issn

1440-1711

pii

icb1015

journal_volume

79

pub_type

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