| dc.creator |
Nombela-Arrieta, César |
|
| dc.creator |
Mempel, Thorsten R. |
|
| dc.creator |
Soriano, Silvia F. |
|
| dc.creator |
Mazo, Irina |
|
| dc.creator |
Wymann, Matthias P. |
|
| dc.creator |
Hirsch, Emilio |
|
| dc.creator |
Martínez-Alonso, Carlos |
|
| dc.creator |
Fukui, Yoshinori |
|
| dc.creator |
Andrian, Ulrich H. von |
|
| dc.creator |
Stein, Jens V. |
|
| dc.date |
2008-03-18T09:55:46Z |
|
| dc.date |
2008-03-18T09:55:46Z |
|
| dc.date |
2007-03 |
|
| dc.date.accessioned |
2017-01-31T01:00:46Z |
|
| dc.date.available |
2017-01-31T01:00:46Z |
|
| dc.identifier |
The Journal of Experimental Medicine, Vol. 204, No. 3, March 19, 2007, pp. 497–510 |
|
| dc.identifier |
1540-9538 |
|
| dc.identifier |
http://hdl.handle.net/10261/3237 |
|
| dc.identifier |
10.1084/jem.20061780 |
|
| dc.identifier.uri |
http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3237 |
|
| dc.description |
Copyright by The Rockefeller University Press |
|
| dc.description |
Recent observations using multiphoton intravital microscopy (MP-IVM) have uncovered an unexpectedly high lymphocyte motility within peripheral lymph nodes (PLNs). Lymphocyteexpressed
intracellular signaling molecules governing interstitial movement remain largely unknown. Here, we used MP-IVM of murine PLNs to examine interstitial motility of lymphocytes lacking the Rac guanine exchange factor DOCK2 and phosphoinositide-3-kinase (PI3Kƴ), signaling molecules that act downstream of G protein–coupled receptors, including chemokine receptors (CKRs). T and B cells lacking DOCK2 alone or DOCK2 and PI3Kƴ displayed markedly reduced motility inside T cell area and B cell follicle, respectively. Lack of PI3Kƴ alone had no effect on migration velocity but resulted in increased turning angles of T cells. As lymphocyte egress from PLNs requires the sphingosine-1-phosphate (S1P) receptor 1, a Gi protein–coupled receptor similar to CKR, we further analyzed whether DOCK2 and PI3Kƴ contributed to S1P-triggered signaling events. S1P-induced cell migration
was signifi cantly reduced in T and B cells lacking DOCK2, whereas T cell–expressed
PI3Kƴ contributed to F-actin polymerization and protein kinase B phosphorylation but not
migration. These fi ndings correlated with delayed lymphocyte egress from PLNs in the
absence of DOCK2 but not PI3K, and a markedly reduced cell motility of DOCK2-defi cient T cells in close proximity to efferent lymphatic vessels. In summary, our data support a central role for DOCK2, and to a lesser extent T cell–expressed PI3Kƴ, for signal transduction during interstitial lymphocyte migration and S1P-mediated egress. |
|
| dc.description |
Peer reviewed |
|
| dc.format |
3186031 bytes |
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| dc.format |
application/pdf |
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| dc.language |
eng |
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| dc.publisher |
Rockefeller University Press |
|
| dc.rights |
openAccess |
|
| dc.subject |
Hematology |
|
| dc.title |
A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate–mediated egress |
|
| dc.type |
Artículo |
|