Tang M L, Hale L P, Steeber D A, Tedder T F
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 1997 Jun 1;158(11):5191-9.
Adhesion of leukocytes to vascular endothelium is crucial for leukocyte migration into tissues. The contributions of L-selectin, P-selectin, and ICAM-1 to interactions between lymphocytes and endothelium was examined using allogeneic skin graft rejection as a model of cutaneous inflammation. L-selectin-deficient (L-selectin(-/-)) mice rejected both primary and secondary allogeneic (BALB/c) skin grafts significantly more slowly than L-selectin(+/+) littermates. Furthermore, skin graft rejection remained significantly delayed in L-selectin(-/-) mice, despite placement of grafts 7 days after i.p. immunization with allogeneic cells, when CTL responses in L-selectin(-/-) mice and L-selectin(+/+) littermates were confirmed to be equivalent. Indeed, specific CTL responses to BALB/c splenocytes were normal or elevated in L-selectin(-/-) mice following either skin grafts or immunization. However, the number of T lymphocytes within allogeneic grafts was lower in L-selectin(-/-) mice as compared with L-selectin(+/+) littermates. Therefore, delayed rejection of skin grafts by L-selectin(-/-) mice reflects impaired migration of effector cells into the graft rather than delayed or impaired generation of a CTL response. In contrast to L-selectin(-/-) mice, P-selectin-deficient and ICAM-1-deficient mice rejected allogeneic skin grafts normally. These findings delineate an important role for L-selectin in lymphocyte recruitment to cutaneous sites of inflammation.
白细胞与血管内皮的黏附对于白细胞迁移到组织中至关重要。以同种异体皮肤移植排斥作为皮肤炎症模型，研究了L-选择素、P-选择素和细胞间黏附分子-1（ICAM-1）在淋巴细胞与内皮细胞相互作用中的作用。L-选择素缺陷（L-selectin(-/-)）小鼠对初次和二次同种异体（BALB/c）皮肤移植的排斥明显比L-选择素(+/+)同窝小鼠缓慢。此外，尽管在用同种异体细胞腹腔内免疫7天后进行移植，L-selectin(-/-)小鼠的皮肤移植排斥仍然明显延迟，此时L-selectin(-/-)小鼠和L-选择素(+/+)同窝小鼠的细胞毒性T淋巴细胞（CTL）反应被证实是等效的。事实上，在进行皮肤移植或免疫后，L-selectin(-/-)小鼠对BALB/c脾细胞的特异性CTL反应正常或增强。然而，与L-选择素(+/+)同窝小鼠相比，L-selectin(-/-)小鼠同种异体移植物中的T淋巴细胞数量较少。因此，L-selectin(-/-)小鼠皮肤移植排斥延迟反映了效应细胞向移植物中的迁移受损，而不是CTL反应的延迟或受损。与L-selectin(-/-)小鼠不同，P-选择素缺陷和ICAM-1缺陷小鼠正常排斥同种异体皮肤移植。这些发现阐明了L-选择素在淋巴细胞募集到皮肤炎症部位中的重要作用。
