In vivo role of adhesion molecules in inflammation induced by immur complex deposition

免疫复合物（IC）的沉积诱导了组织损伤的急性炎症反应。IC诱导的炎症由炎性细胞浸润介导，这是一个受多种粘附分子表达高度调节的过程。为了评估L-选择素和细胞间粘附分子-1（ICAM-1）在这一发病过程中的作用，在缺乏L-选择素（L-选择素-/-）、ICAM-1（ICAM-1-/*）或两者（L-选择素/ICAM-1-/-）的小鼠中检测了皮肤炎症被动Arthus反应。与野生型同窝小鼠相比，L-选择素-/-、ICAM-1-/-和L-选择素/ICAM* 1-/-小鼠的水肿和出血（分别在 * 激发后4小时和8小时达到峰值）显著减少。一般来说，ICAM-1-/-小鼠的水肿和出血比L-选择素-A小鼠的水肿和出血更少，但与ICAM-1-/-或L-选择素-/-小鼠相比，L-选择素/ICAM-1-/-小鼠的水肿和出血减少最显著。在所有adhesi* 分子缺陷小鼠中，水肿和出血减少与中性粒细胞和肥大细胞浸润减少相关，但在L-选择素/ICAM-1-/-小鼠中，白细胞浸润受影响最大。在腹膜Arthus反应中，所有突变小鼠也观察到中性粒细胞和肥大细胞浸润减少。此外，ea* 缺陷小鼠皮肤肿瘤坏死因子-a的产生受到抑制，这与皮肤炎症的减少有关。这些结果表明，ICAM-1和L-选择素协同促进皮肤Arthus反应，调节中性粒细胞和肥大细胞募集，并表明ICAM-1和L-选择素是人类IC介导疾病的治疗靶点。

The deposition of immune complexes (IC) induces an acute inflammatory response with tiss* injury. IC-induced inflammation is mediated by inflammatory cell infiltration, a process high* regulated by expression of multiple adhesion molecules. To assess the role of L-selectin ar* intercellular adhesion molecule-1 (ICAM-1) in this pathogenetic process, the cutaneous rever* passive Arthus reaction was examined in mice lacking L-selectin (L-selectin-/-), ICAM-1 (ICAM-1-/* or both (L-selectin/ICAM-1-/-). Edema and hemorrhage, which peaked 4 and 8 hours after * challenge respectively, were significantly reduced in L-selectin-/-, ICAM-1-/-, and L-selectin/ICAM* 1-/- mice compared with wild type littermates. In general, edema and hemorrhage were mo significantly inhibited in ICAM-1-/- mice than in L-selectin-A mice, but were most significant* reduced in L-selectin/ICAM-1-/- mice compared with ICAM-1-/- or L-selectin-/- mice. Decrease edema and hemorrhage correlated with reduced neutrophil and mast cell infiltration in all adhesi* molecule-deficient mice, but leukocyte infiltration was most affected in L-selectin/ICAM-1-/- mic Reduced neutrophil and mast cell infiltration was also observed for all mutant mice in the peritone Arthus reaction. Furthermore, cutaneous tumor necrosis factor-a production was inhibited in ea* deficient mouse, which paralleled the reductions in cutaneous inflammation. These resu* indicate that ICAM-1 and L-selectin cooperatively contribute to the cutaneous Arthus reaction * regulating neutrophii and mast cell recruitment and suggest that ICAM-1 and L-selectin a therapeutic targets for human IC-mediated disease.