Table 1.
Transcellular transendothelial cell migration in vitro. In vitro studies enable closer examination of, and interventions into the sub-cellular processes which mediate transcellular transmigration. This table summarises in vitro work in the field and gives the key mechanisms that have been identified. Abbreviations: Human umbilical vein endothelial cells (HUVEC); Human dermal microvascular endothelial cells (HDMVEC); Human lung microvascular endothelial cells (HLMVEC); Human coronary artery endothelial cells (HCAEC.); Murine brain-derived endothelial cell line (bEnd.3)
| Model | Leukocyte | Frequency of TEM and key mechanistic insights |
Ref |
|---|---|---|---|
| Flow model using TNFα-activated (24h) HUVEC, followed by PAF (5 min). |
PMN | 5% transcellular TEM. | 11 |
| Static model using TNFα-activated (12h) HUVEC, followed by PAF, MCP-1 or SDF-1 (20 min). |
Monocytes, PMN & lymphocytes |
7%, 5% and 11% transcellular TEM of monocytes, PMN, and lymphocytes, respectively. Paracellular and transcellular migration is associated with ICAM-1 enriched docking structures. |
12 |
| Flow model using TNFα-activated (24h) HUVEC. |
PMN | 15% transcellular TEM. ICAM-1 promotes junctional and non-junctional TEM via distinct cytoplasmic tail associations. |
13 |
| Static model using IL-1β-activated (12h) HCAEC |
Monocytes | 10 % transcellular TEM. IL-1β stimulation disrupts adherens junctions and facilitates paracellular TEM. |
14 |
| Flow model using TNFα-activated (4h) HUVEC. |
PMN & monocytes |
Monocytes preferentially use the transcellular route, which is facilitated by the vimentin intermediate filament network. |
15 |
| Static model using TNFα-activated (15h) HUVEC or HDMVEC. |
T- Lymphoblasts |
9% transcellular TEM of HUVEC, 30 % HDMVEC. Cavaeolin-1 mediates the translocation of ICAM-1 to cavaolae and F-actin rich domains. |
16 |
| Static model using TNFα-activated (12h) HUVEC or HDMVEC, and HLMVEC |
Lymphocytes | 10% transcellular TEM on HUVEC, ~30% on microvascular EC. Transcellular migration is initiated by Src dependent invasive podosomes and involves SNARE mediated membrane fusion events to create a transcellular pore. |
17 |
| Static model using TNFα-activated (12h) HDMVEC. |
PMN | 30% transcellular TEM (reduced to 10% upon inhibition of caveolin function). Caveolin function is associated with transcellular TEM. |
18 |
| Static model using TNFα-activated HDMEC. |
PMN | 25% transcellular TEM. | 19 |
| Static model using TNFα-activated (16h) bEnd.3 cells, plus SDF-1. |
T cells | 5 % transcellular TEM (increases to 30% upon inhibition of PKC/etc signalling). T-cell polarisation and crawling utilises PKCζ/Tiam1/Rac signalling, and inhibition of this increases transcellular TEM. |
20* |
| Static model using TNFα-activated (4h) HUVEC. |
Lymphocytes | Membrane expressed PV-1, and intracellular vimentin and caveolin-1 in EC facilitates the formation of transcellular channels for migrating lymphocytess |
21 |