---
_id: '3392'
abstract:
- lang: eng
text: Migrating lymphocytes acquire a polarized phenotype with a leading and a trailing
edge, or uropod. Although in vitro experiments in cell lines or activated primary
cell cultures have established that Rho-p160 coiled-coil kinase (ROCK)-myosin
II-mediated uropod contractility is required for integrin de-adhesion on two-dimensional
surfaces and nuclear propulsion through narrow pores in three-dimensional matrices,
less is known about the role of these two events during the recirculation of primary,
nonactivated lymphocytes. Using pharmacological antagonists of ROCK and myosin
II, we report that inhibition of uropod contractility blocked integrin-independent
mouse T cell migration through narrow, but not large, pores in vitro. T cell crawling
on chemokine-coated endothelial cells under shear was severely impaired by ROCK
inhibition, whereas transendothelial migration was only reduced through endothelial
cells with high, but not low, barrier properties. Using three-dimensional thick-tissue
imaging and dynamic two-photon microscopy of T cell motility in lymphoid tissue,
we demonstrated a significant role for uropod contractility in intraluminal crawling
and transendothelial migration through lymph node, but not bone marrow, endothelial
cells. Finally, we demonstrated that ICAM-1, but not anatomical constraints or
integrin-independent interactions, reduced parenchymal motility of inhibitor-treated
T cells within the dense lymphoid microenvironment, thus assigning context-dependent
roles for uropod contraction during lymphocyte recirculation.
article_processing_charge: No
article_type: original
author:
- first_name: Silvia
full_name: Soriano, Silvia
last_name: Soriano
- first_name: Miroslav
full_name: Hons, Miroslav
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Kathrin
full_name: Schumann, Kathrin
last_name: Schumann
- first_name: Varsha
full_name: Kumar, Varsha
last_name: Kumar
- first_name: Timo
full_name: Dennier, Timo
last_name: Dennier
- first_name: Ruth
full_name: Lyck, Ruth
last_name: Lyck
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Jens
full_name: Stein, Jens
last_name: Stein
citation:
ama: Soriano S, Hons M, Schumann K, et al. In vivo analysis of uropod function during
physiological T cell trafficking. Journal of Immunology. 2011;187(5):2356-2364.
doi:10.4049/jimmunol.1100935
apa: Soriano, S., Hons, M., Schumann, K., Kumar, V., Dennier, T., Lyck, R., … Stein,
J. (2011). In vivo analysis of uropod function during physiological T cell trafficking.
Journal of Immunology. American Association of Immunologists. https://doi.org/10.4049/jimmunol.1100935
chicago: Soriano, Silvia, Miroslav Hons, Kathrin Schumann, Varsha Kumar, Timo Dennier,
Ruth Lyck, Michael K Sixt, and Jens Stein. “In Vivo Analysis of Uropod Function
during Physiological T Cell Trafficking.” Journal of Immunology. American
Association of Immunologists, 2011. https://doi.org/10.4049/jimmunol.1100935.
ieee: S. Soriano et al., “In vivo analysis of uropod function during physiological
T cell trafficking,” Journal of Immunology, vol. 187, no. 5. American Association
of Immunologists, pp. 2356–2364, 2011.
ista: Soriano S, Hons M, Schumann K, Kumar V, Dennier T, Lyck R, Sixt MK, Stein
J. 2011. In vivo analysis of uropod function during physiological T cell trafficking.
Journal of Immunology. 187(5), 2356–2364.
mla: Soriano, Silvia, et al. “In Vivo Analysis of Uropod Function during Physiological
T Cell Trafficking.” Journal of Immunology, vol. 187, no. 5, American Association
of Immunologists, 2011, pp. 2356–64, doi:10.4049/jimmunol.1100935.
short: S. Soriano, M. Hons, K. Schumann, V. Kumar, T. Dennier, R. Lyck, M.K. Sixt,
J. Stein, Journal of Immunology 187 (2011) 2356–2364.
date_created: 2018-12-11T12:03:04Z
date_published: 2011-09-01T00:00:00Z
date_updated: 2025-09-30T08:43:55Z
day: '01'
department:
- _id: MiSi
doi: 10.4049/jimmunol.1100935
external_id:
isi:
- '000294059500040'
intvolume: ' 187'
isi: 1
issue: '5'
language:
- iso: eng
month: '09'
oa_version: None
page: 2356 - 2364
publication: Journal of Immunology
publication_identifier:
eissn:
- 1550-6606
issn:
- 0022-1767
publication_status: published
publisher: American Association of Immunologists
publist_id: '3215'
quality_controlled: '1'
scopus_import: '1'
status: public
title: In vivo analysis of uropod function during physiological T cell trafficking
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 187
year: '2011'
...
---
_id: '3927'
abstract:
- lang: eng
text: TNF-alpha has been clearly identified as central mediator of T cell activation-induced
acute hepatic injury in mice, e.g., Con A hepatitis. In this model, liver injury
depends on both TNFRs, i.e., the 55-kDa TNFR1 as well as the 75-kDa TNFR2. We
show in this report that the hepatic TNFRs are not transcriptionally regulated,
but are regulated by receptor shedding. TNF directly mediates hepatocellular death
by activation of TNFR1 but also induces the expression of inflammatory proteins,
such as cytokines and adhesion molecules. Here we provide evidence that resistance
of TNFR1(-/-) and TNFR2(-/-) mice against Con A hepatitis is not due to an impaired
production of the central mediators TNF and IFN-gamma. Con A injection results
in a massive induction of ICAM-1, VCAM-1, and E-selectin in the liver. Lack of
either one of both TNFRs did not change adhesion molecule expression in the livers
of Con A-treated mice, presumably reflecting the fact that other endothelial cell-activating
cytokines up-regulated adhesion molecule expression. However, treatment of TNFR1(-/-)
and TNFR2(-/-) mice with murine rTNF revealed a predominant role for TNFR1 for
the induction of hepatic adhesion molecule expression. Pretreatment with blocking
Abs against E- and P-selectin or of ICAM(-/-) mice with anti-VCAM-1 Abs failed
to prevent Con A hepatitis, although accumulation of the critical cell population,
i.e., CD4(+) T cells was significantly inhibited. Hence, up-regulation of adhesion
molecules during acute hepatitis unlikely contributes to organ injury but rather
represents a defense mechanism.
acknowledgement: We thank Dr. H. Bluethmann (F. Hoffmann-LaRoche AG, Basle, Switzerland)
for kindly providing us TNFR knockout mice. We are indebted to Dr. G. R. Adolf (Bender
& Co Vienna, Austria) for providing recombinant murine TNF. We are also indebted
to Dr. D. Vestweber for providing anti-P-selectin mAb (23). We thank Dr. W. Neuhuber
(Institute of Anatomy, University of Erlangen-NÜrnberg, Erlangen, Germany) for
experimental support regarding confocal laser scanning microscopy. The perfect technical
assistance of Andrea Agli is gratefully acknowledged.
article_processing_charge: No
article_type: original
author:
- first_name: Dominik
full_name: Wolf, Dominik
last_name: Wolf
- first_name: Rupert
full_name: Hallmann, Rupert
last_name: Hallmann
- first_name: Gabriele
full_name: Sass, Gabriele
last_name: Sass
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Sabine
full_name: Küsters, Sabine
last_name: Küsters
- first_name: Bastian
full_name: Fregien, Bastian
last_name: Fregien
- first_name: Christian
full_name: Trautwein, Christian
last_name: Trautwein
- first_name: Gisa
full_name: Tiegs, Gisa
last_name: Tiegs
citation:
ama: Wolf D, Hallmann R, Sass G, et al. TNF-α-induced expression of adhesion molecules
in the liver is under the control of TNFR1--relevance for concanavalin A-induced
hepatitis. Journal of Immunology. 2001;166(2):1300-1307. doi:10.4049/jimmunol.166.2.1300
apa: Wolf, D., Hallmann, R., Sass, G., Sixt, M. K., Küsters, S., Fregien, B., …
Tiegs, G. (2001). TNF-α-induced expression of adhesion molecules in the liver
is under the control of TNFR1--relevance for concanavalin A-induced hepatitis.
Journal of Immunology. American Association of Immunologists. https://doi.org/10.4049/jimmunol.166.2.1300
chicago: Wolf, Dominik, Rupert Hallmann, Gabriele Sass, Michael K Sixt, Sabine Küsters,
Bastian Fregien, Christian Trautwein, and Gisa Tiegs. “TNF-α-Induced Expression
of Adhesion Molecules in the Liver Is under the Control of TNFR1--Relevance for
Concanavalin A-Induced Hepatitis.” Journal of Immunology. American Association
of Immunologists, 2001. https://doi.org/10.4049/jimmunol.166.2.1300.
ieee: D. Wolf et al., “TNF-α-induced expression of adhesion molecules in
the liver is under the control of TNFR1--relevance for concanavalin A-induced
hepatitis,” Journal of Immunology, vol. 166, no. 2. American Association
of Immunologists, pp. 1300–1307, 2001.
ista: Wolf D, Hallmann R, Sass G, Sixt MK, Küsters S, Fregien B, Trautwein C, Tiegs
G. 2001. TNF-α-induced expression of adhesion molecules in the liver is under
the control of TNFR1--relevance for concanavalin A-induced hepatitis. Journal
of Immunology. 166(2), 1300–1307.
mla: Wolf, Dominik, et al. “TNF-α-Induced Expression of Adhesion Molecules in the
Liver Is under the Control of TNFR1--Relevance for Concanavalin A-Induced Hepatitis.”
Journal of Immunology, vol. 166, no. 2, American Association of Immunologists,
2001, pp. 1300–07, doi:10.4049/jimmunol.166.2.1300.
short: D. Wolf, R. Hallmann, G. Sass, M.K. Sixt, S. Küsters, B. Fregien, C. Trautwein,
G. Tiegs, Journal of Immunology 166 (2001) 1300–1307.
date_created: 2018-12-11T12:05:56Z
date_published: 2001-01-15T00:00:00Z
date_updated: 2023-05-11T13:37:29Z
day: '15'
doi: 10.4049/jimmunol.166.2.1300
extern: '1'
external_id:
pmid:
- '11145713'
intvolume: ' 166'
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://www.jimmunol.org/content/166/2/1300.long
month: '01'
oa: 1
oa_version: None
page: 1300 - 1307
pmid: 1
publication: Journal of Immunology
publication_identifier:
issn:
- 0022-1767
publication_status: published
publisher: American Association of Immunologists
publist_id: '2200'
quality_controlled: '1'
status: public
title: TNF-α-induced expression of adhesion molecules in the liver is under the control
of TNFR1--relevance for concanavalin A-induced hepatitis
type: journal_article
user_id: ea97e931-d5af-11eb-85d4-e6957dddbf17
volume: 166
year: '2001'
...