Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1 adhesion pathways.

Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1 adhesion pathways.
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DOI:
10.1084/jem.20010685
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发表时间:
2003-05-19
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Michie SA
Michie SA
中科院分区:
其他
文献类型:
--
作者:
Xu B;Wagner N;Pham LN;Magno V;Shan Z;Butcher EC;Michie SA

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支气管相关淋巴组织(BALT)参与气道免疫反应。然而,人们对淋巴细胞-内皮粘附级联反应知之甚少,该反应可将血液中的淋巴细胞招募到BALT中。我们发现BALT的高内皮小静脉(hev)表达大量的VCAM-1,与其他次级淋巴组织的hev形成明显对比。BALT hev也表达l -选择素配体PNAd。抗l -选择素、抗pnad和抗lfa -1单克隆抗体几乎完全阻断B淋巴细胞和T淋巴细胞对BALT的归巢,而抗α4整合素和抗vcam -1单克隆抗体则抑制了近40%的归巢。α4β7整合素和MAdCAM-1不参与。重要的是,我们发现针对α4整合素和VCAM-1的单克隆抗体可显著阻止总T细胞(80%记忆表型)向BALT的迁移,而非初始T细胞和B细胞。这些结果表明,包括l -选择素/PNAd、α4β1整合素/VCAM-1和LFA-1在内的粘附级联可靶向BALT的特定淋巴细胞亚群。α4β1整合素/VCAM-1的高水平参与在继发淋巴组织中是独特的,可能有助于统一BALT和其他支气管肺组织的淋巴细胞迁移途径和免疫反应。
Bronchus-associated lymphoid tissue (BALT) participates in airway immune responses. However, little is known about the lymphocyte–endothelial adhesion cascades that recruit lymphocytes from blood into BALT. We show that high endothelial venules (HEVs) in BALT express substantial levels of VCAM-1, in marked contrast to HEVs in other secondary lymphoid tissues. BALT HEVs also express the L-selectin ligand PNAd. Anti–L-selectin, anti-PNAd, and anti–LFA-1 mAbs almost completely block the homing of B and T lymphocytes into BALT, whereas anti–α4 integrin and anti–VCAM-1 mAbs inhibit homing by nearly 40%. α4β7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against α4 integrin and VCAM-1 significantly block the migration of total T cells (80% memory phenotype) but not naive T and B cells to BALT. These results suggest that an adhesion cascade, which includes L-selectin/PNAd, α4β1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of α4β1 integrin/VCAM-1 is unique among secondary lymphoid tissues, and may help unify lymphocyte migration pathways and immune responses in BALT and other bronchopulmonary tissues.
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