Andrew D P, Spellberg J P, Takimoto H, Schmits R, Mak T W, Zukowski M M
Amgen Inc., Boulder, USA.
Eur J Immunol. 1998 Jun;28(6):1959-69. doi: 10.1002/(SICI)1521-4141(199806)28:06<1959::AID-IMMU1959>3.0.CO;2-4.
The leukocyte integrin LFA-1 plays an important role in leukocyte trafficking and the immune response. Using LFA-1-deficient mice, we demonstrate that LFA-1 regulates the trafficking of lymphocytes to peripheral lymph nodes, and, to a lesser degree, to mesenteric lymph nodes and acute inflammatory sites. LFA-1, either because of its role in initial adhesion and/ or the passage of leukocytes across endothelial cells, plays a vital role in T lymphocyte and neutrophil transendothelial migration. Neutrophils and activated T lymphocytes from LFA-1-deficient mice were unable to cross endothelial cell monolayers in response to a chemokine gradient, whereas wild-type (WT) T lymphocytes and neutrophils were capable of migration. By contrast, LFA-1-deficient T lymphocytes displayed normal chemotaxis to the same chemokine. Our studies with LFA-1-deficient monocytes indicate that LFA-1 acts in concert with complement receptor 3 to mediate transendothelial migration of these cells, as anti-CD18 monoclonal antibodies (mAb) blocked both WT and LFA-1-deficient monocyte transendothelial migration, whereas anti-CD11 b mAb preferentially blocked transendothelial migration of LFA-1-deficient monocytes. Finally, whereas anti-CD31 mAb blocked WT monocyte and neutrophil transendothelial cell migration they did not block LFA-1-deficient monocyte and neutrophil transendothelial migration.
白细胞整合素淋巴细胞功能相关抗原-1（LFA-1）在白细胞转运和免疫反应中发挥重要作用。利用LFA-1缺陷小鼠，我们证明LFA-1调节淋巴细胞向外周淋巴结的转运，在较小程度上也调节向肠系膜淋巴结和急性炎症部位的转运。LFA-1因其在初始黏附以及白细胞穿过内皮细胞过程中的作用，在T淋巴细胞和中性粒细胞跨内皮迁移中发挥关键作用。来自LFA-1缺陷小鼠的中性粒细胞和活化T淋巴细胞无法响应趋化因子梯度穿过内皮细胞单层，而野生型（WT）T淋巴细胞和中性粒细胞能够迁移。相比之下，LFA-1缺陷的T淋巴细胞对相同趋化因子表现出正常的趋化性。我们对LFA-1缺陷单核细胞的研究表明，LFA-1与补体受体3协同作用介导这些细胞的跨内皮迁移，因为抗CD18单克隆抗体（mAb）阻断了WT和LFA-1缺陷单核细胞的跨内皮迁移，而抗CD11b mAb优先阻断LFA-1缺陷单核细胞的跨内皮迁移。最后，抗CD31 mAb阻断WT单核细胞和中性粒细胞的跨内皮细胞迁移，但不阻断LFA-1缺陷单核细胞和中性粒细胞的跨内皮迁移。
