| 2. |
- Qian, Hong, et al.
(författare)
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Distinct roles of integrins {alpha}6 and {alpha}4 in homing of fetal liver hematopoietic stem and progenitor cells.
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 110:7, s. 2399-2407
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Tidskriftsartikel (refereegranskat)abstract
- Homing of hematopoietic stem cells (HSCs) into the bone marrow (BM) is a prerequisite for establishment of hematopoiesis during development and following transplantation. However, the molecular interactions that control homing of HSCs, in particular, of fetal HSCs, are not well understood. Herein, we studied the role of the alpha 6 and alpha A integrin receptors for homing and engraftment of fetal liver (FL) HSCs and hernatopoietic progenitor cells (HPCs) to adult BM by using integrin alpha 6 gene-deleted mice and functionblocking antibodies. Both integrins were ubiquitously expressed in FL Lin(-)Sca1 (+)Kit(+) (LSK) cells. Deletion of integrin alpha 6 receptor or inhibition by a functionblocking antibody inhibited FL LSK cell adhesion to its extracellular ligands, laminins-411 and -511 in vitro, and significantly reduced homing of HPCs to BM. In contrast, the anti-integrin alpha 6 antibody did not inhibit BM homing of HSCs. In agreement with this, integrin alpha 6 gene-deleted FL HSCs did not display any homing or engraftment defect compared with wildtype littermates. In contrast, inhibition of integrin alpha 4 receptor by a functionblocking antibody virtually abrogated homing of both FL HSCs and HPCs to BM, indicating distinct functions for integrin alpha 6 and alpha 4 receptors during homing of fetal HSCs and HPCs.
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| 3. |
- Wu, Chuan, et al.
(författare)
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Endothelial basement membrane laminin alpha 5 selectively inhibits T lymphocyte extravasation into the brain
- 2009
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 15:5, s. 519-527
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Tidskriftsartikel (refereegranskat)abstract
- Specific inhibition of the entry of encephalitogenic T lymphocytes into the central nervous system in multiple sclerosis would provide a means of inhibiting disease without compromising innate immune responses. We show here that targeting lymphocyte interactions with endothelial basement membrane laminins provides such a possibility. In mouse experimental autoimmune encephalomyelitis, T lymphocyte extravasation correlates with sites expressing laminin alpha 4 and small amounts of laminin alpha 5. In mice lacking laminin alpha 4, laminin alpha 5 is ubiquitously expressed along the vascular tree, resulting in marked and selective reduction of T lymphocyte infiltration into the brain and reduced disease susceptibility and severity. Vessel phenotype and immune response were not affected in these mice. Rather, laminin alpha 5 directly inhibited integrin alpha(6)beta(1)-mediated migration of T lymphocytes through laminin alpha 4. The data indicate that T lymphocytes use mechanisms distinct from other immune cells to penetrate the endothelial basement membrane barrier, permitting specific targeting of this immune cell population.
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