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http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3237| Title: | A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate–mediated egress |
| Keywords: | Hematology |
| Publisher: | Rockefeller University Press |
| Description: | Copyright by The Rockefeller University Press 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. Peer reviewed |
| URI: | http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3237 |
| Other Identifiers: | The Journal of Experimental Medicine, Vol. 204, No. 3, March 19, 2007, pp. 497–510 1540-9538 http://hdl.handle.net/10261/3237 10.1084/jem.20061780 |
| Appears in Collections: | Digital Csic |
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