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A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them.

Carman CV, Springer TA - J. Cell Biol. (2004)

Bottom Line: We provide definitive evidence for transcellular (i.e., through individual endothelial cells) diapedesis in vitro and demonstrate that virtually all, both para- and transcellular, diapedesis occurs in the context of a novel "cuplike" transmigratory structure.Disruption of projections was highly correlated with inhibition of transmigration.These findings suggest a novel mechanism, the "transmigratory cup", by which the endothelium provides directional guidance to leukocytes for extravasation.

View Article: PubMed Central - PubMed

Affiliation: The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

ABSTRACT
The basic route and mechanisms for leukocyte migration across the endothelium remain poorly defined. We provide definitive evidence for transcellular (i.e., through individual endothelial cells) diapedesis in vitro and demonstrate that virtually all, both para- and transcellular, diapedesis occurs in the context of a novel "cuplike" transmigratory structure. This endothelial structure was comprised of highly intercellular adhesion molecule-1- and vascular cell adhesion molecule-1-enriched vertical microvilli-like projections that surrounded transmigrating leukocytes and drove redistribution of their integrins into linear tracks oriented parallel to the direction of diapedesis. Disruption of projections was highly correlated with inhibition of transmigration. These findings suggest a novel mechanism, the "transmigratory cup", by which the endothelium provides directional guidance to leukocytes for extravasation.

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Caveolin-1 is partially associated with the transcellular migration pore. Human lymphocytes were incubated for 10 min with TNF-α–activated, SDF-1–pretreated HUVECs transfected with either caveolin-1-GFP (A and B) or GFP-caveolin-1 (C and D) followed by fixation and staining. β2 (blue), ICAM-1 (IC1; red), and caveolin-1 (cav-1; green) are shown for representative transcellular migration events. Confocal sections that encompass the TEM passage (Fig.1, F and H) are projected as top views. Bar, 5 μm.
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fig3: Caveolin-1 is partially associated with the transcellular migration pore. Human lymphocytes were incubated for 10 min with TNF-α–activated, SDF-1–pretreated HUVECs transfected with either caveolin-1-GFP (A and B) or GFP-caveolin-1 (C and D) followed by fixation and staining. β2 (blue), ICAM-1 (IC1; red), and caveolin-1 (cav-1; green) are shown for representative transcellular migration events. Confocal sections that encompass the TEM passage (Fig.1, F and H) are projected as top views. Bar, 5 μm.

Mentions: The nature of the transcellular pore itself remains to be elucidated. However, as an initial step, we characterized the distribution of endothelial caveolin-1, a structural constituent of caveolea. These experiments demonstrate a partial, nonetheless unambiguous, association of caveolin-1 with the transcellular pore (Fig. 3), which is consistent with a potential relationship between caveolae and pore formation.


A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them.

Carman CV, Springer TA - J. Cell Biol. (2004)

Caveolin-1 is partially associated with the transcellular migration pore. Human lymphocytes were incubated for 10 min with TNF-α–activated, SDF-1–pretreated HUVECs transfected with either caveolin-1-GFP (A and B) or GFP-caveolin-1 (C and D) followed by fixation and staining. β2 (blue), ICAM-1 (IC1; red), and caveolin-1 (cav-1; green) are shown for representative transcellular migration events. Confocal sections that encompass the TEM passage (Fig.1, F and H) are projected as top views. Bar, 5 μm.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172560&req=5

fig3: Caveolin-1 is partially associated with the transcellular migration pore. Human lymphocytes were incubated for 10 min with TNF-α–activated, SDF-1–pretreated HUVECs transfected with either caveolin-1-GFP (A and B) or GFP-caveolin-1 (C and D) followed by fixation and staining. β2 (blue), ICAM-1 (IC1; red), and caveolin-1 (cav-1; green) are shown for representative transcellular migration events. Confocal sections that encompass the TEM passage (Fig.1, F and H) are projected as top views. Bar, 5 μm.
Mentions: The nature of the transcellular pore itself remains to be elucidated. However, as an initial step, we characterized the distribution of endothelial caveolin-1, a structural constituent of caveolea. These experiments demonstrate a partial, nonetheless unambiguous, association of caveolin-1 with the transcellular pore (Fig. 3), which is consistent with a potential relationship between caveolae and pore formation.

Bottom Line: We provide definitive evidence for transcellular (i.e., through individual endothelial cells) diapedesis in vitro and demonstrate that virtually all, both para- and transcellular, diapedesis occurs in the context of a novel "cuplike" transmigratory structure.Disruption of projections was highly correlated with inhibition of transmigration.These findings suggest a novel mechanism, the "transmigratory cup", by which the endothelium provides directional guidance to leukocytes for extravasation.

View Article: PubMed Central - PubMed

Affiliation: The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

ABSTRACT
The basic route and mechanisms for leukocyte migration across the endothelium remain poorly defined. We provide definitive evidence for transcellular (i.e., through individual endothelial cells) diapedesis in vitro and demonstrate that virtually all, both para- and transcellular, diapedesis occurs in the context of a novel "cuplike" transmigratory structure. This endothelial structure was comprised of highly intercellular adhesion molecule-1- and vascular cell adhesion molecule-1-enriched vertical microvilli-like projections that surrounded transmigrating leukocytes and drove redistribution of their integrins into linear tracks oriented parallel to the direction of diapedesis. Disruption of projections was highly correlated with inhibition of transmigration. These findings suggest a novel mechanism, the "transmigratory cup", by which the endothelium provides directional guidance to leukocytes for extravasation.

Show MeSH
Related in: MedlinePlus