l-selectin and alpha4beta7 integrin, but not ICAM-1, regulate lymphocyte distribution in gut-associated lymphoid tissue of mice.
l-selectin and alpha4beta7 integrin, but not ICAM-1, regulate lymphocyte distribution in gut-associated lymphoid tissue of mice.
复制标题
L-选择素和 α4β7 整合素（但不是 ICAM-1）调节小鼠肠道相关淋巴组织中的淋巴细胞分布。
DOI：
10.1016/j.surg.2004.08.003
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Ikeda,Shigeo
中科院分区：
文献类型：
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作者：
Reese,ShannonR;Kudsk,KennethA;Genton,Laurence;Ikeda,Shigeo
背景淋巴细胞(L-选择素和α-4、β-7)和内皮细胞(MAdCAM1和ICAM-1)上的黏附分子可将淋巴细胞定向进入小鼠肠相关淋巴组织(GALT)。肠外营养和MAdCAM-1阻断可减少GALT细胞质量。[方法]实验一采用流式细胞术检测α-选择素、β-7和α-4β-7在喂养小鼠体内的表达。在实验2中，49只小鼠随机接受食物、肠外营养、食物+静脉(IV)抗CD62L、食物+IV抗LPAM-1、或食物+IV亚型对照抗体。4天后测定淋巴细胞GALT产量及呼吸道和肠道IgA水平。在实验3中，27只小鼠随机接受5天的饮食、肠外营养、Chw+IV抗ICAM-1单抗或Chw+IV亚型对照抗体。结果80%的外周血淋巴细胞L-选择素和α-4β-7呈阳性反应。L-选择素和α-4β-7阻断组派耶氏斑、固有层和上皮内间隙的淋巴细胞计数(分别为3.1、1.8和0.9×10 6和2.1、1.9和0.7×10 6)均低于饲料组(5.9、3.0和1.7×10 6；P<；.0 2与L-选择素组和P<；.001vsα4β7组)，并与静脉注射组的水平相似。除非肠外营养组(P<；0.04vs食物组)外，所有组的呼吸系统和肠道免疫球蛋白A水平均保持不变。ICAM-1阻断不影响细胞计数和IgA水平。结论大多数循环淋巴细胞具有GALT归巢潜能。其分布可被L-选择素或α-4β-7阻断，但不受ICAM-1的影响。
BACKGROUNDAdhesion molecules on lymphocytes (l-selectin and α4β7) and endothelium (MAdCAM-1 and ICAM-1) direct lymphocytes into the gut-associated lymphoid tissue (GALT) of mice. Parenteral nutrition and MAdCAM-1 blockade reduce GALT cell mass. This study examined the effects on GALT cell mass of blockade of l-selectin, α4β7, and ICAM-1 with saturating doses of monoclonal antibodies.METHODSIn experiment 1, l-selectin and α4β7 expression were measured by flow cytometry in chow-fed mice. In experiment 2, 49 mice randomly received chow, parenteral nutrition, chow+intravenous (IV) anti-CD62L, chow+IV anti-LPAM-1, or chow+IV isotype control antibody. After 4 days, lymphocyte yields in GALT and respiratory and intestinal IgA levels were measured. In experiment 3, 27 mice randomly received chow, parenteral nutrition, chow+IV anti-ICAM-1 monoclonal antibody, or chow+IV isotype control antibody for 5 days. Lymphocyte counts and IgA levels were determined as in experiment 2.RESULTSSome 80% of all circulating lymphocytes were positive for l-selectin and α4β7. Lymphocyte counts in the Peyer's patches, lamina propria, and intraepithelial space were lower in the l-selectin and α4β7 blockade groups (3.1, 1.8, and 0.9 × 106and 2.1, 1.9, and 0.7 × 106, respectively) than in the chow group (5.9, 3.0, and 1.7 × 106; P < .02 vs the l-selectin group and P <.001 vs the α4β7 group) and similar to the levels in the parenteral group. Respiratory and intestinal IgA levels are maintained in all groups except the parenteral group (P<.04 vs the chow group). ICAM-1 blockade did not influence cell counts or IgA levels.CONCLUSIONMost circulating lymphocytes have GALT homing potential. Their distribution into GALT is hindered by blockade of l-selectin or α4β7, but not by ICAM-1.