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JCS ePress
online publication date 19 Apr 2005
doi: 10.1242/jcs.02340
Research Article
PECAM-1,
6 integrins and neutrophil elastase co-operate in mediating neutrophil transmigration
Shijun Wang,
John P. Dangerfield,
Rebecca E. Young,
and
Sussan Nourshargh*
* Author for correspondence (e-mail: s.nourshargh{at}imperial.ac.uk)
The heterogeneous nature of the perivascular basement membrane (composed primarily of laminin and collagen type IV) suggests the existence of an elaborate array of adhesive interactions and possibly proteolytic events in leukocyte migration through this barrier. In this context, blockade of
6 integrins (laminin receptors), neutrophil elastase (NE) or both inhibited neutrophil migration through interleukin-1
(IL-1
)-stimulated mouse cremasteric venules, as observed by intravital microscopy. Furthermore, analysis of tissues by confocal microscopy indicated a synergistic role for
6 integrins and NE in mediating neutrophil migration through the perivascular basement membrane. Using a combined in vitro and in vivo experimental approach, the findings of this study also suggest that
6 integrins and NE are mobilized from intracellular stores to the cell surface of transmigrating mouse neutrophils, although these events occur via mechanisms dependent on and independent of platelet/endothelial-cell adhesion molecule 1 (PECAM-1, CD31), respectively. Despite different regulatory mechanisms, blockade of
6 integrins or NE inhibited migration of murine neutrophils through laminin-coated filters in vitro. Collectively, the findings suggest that, whereas regulation of the expression of
6 integrins and NE occur via different adhesive mechanisms, these molecules might act in a co-operative manner in mediating neutrophil migration through venular walls, in particular the perivascular basement membrane.
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