Christofidou-Solomidou M, Murphy G F, Albelda S M
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
Am J Pathol. 1996 Jan;148(1):177-88.
Previous in vitro data indicate that degranulation of human mast cells triggers the induction of endothelial molecules important in leukocyte adhesion. In vivo experimental systems have not previously existed, however, to determine whether human mast cell degranulation is sufficient stimulus for leukocyte recruitment. To study this question, neonatal foreskins were transplanted onto immunodeficient mice. The grafts contained physiological numbers of human dermal mast cells that could be degranulated by a number of secretagogues that activate mast cells by different mechanisms. Degranulation was associated with an inflammatory response characterized by edema, up-regulation primarily of microvessel E-selectin, and influx of neutrophils. Leukocyte emigration associated with mast cell degranulation was inhibited by a monoclonal antibody against human E-selectin. These data indicate that degranulation of human mast cells in the human/SCID mouse model provokes cellular inflammation in skin. The ability to significantly inhibit early leukocyte infiltration with an antibody against E-selectin in this model supports the hypothesis that this molecule plays an important role in mast-cell-induced inflammation.
先前的体外数据表明，人肥大细胞脱颗粒会触发对白细胞黏附至关重要的内皮分子的诱导。然而，此前尚未存在体内实验系统来确定人肥大细胞脱颗粒是否足以刺激白细胞募集。为研究这个问题，将新生儿包皮移植到免疫缺陷小鼠身上。移植组织中含有生理数量的人真皮肥大细胞，这些肥大细胞可被多种通过不同机制激活肥大细胞的促分泌剂诱导脱颗粒。脱颗粒与以水肿、主要是微血管E选择素上调以及中性粒细胞流入为特征的炎症反应相关。针对人E选择素的单克隆抗体可抑制与肥大细胞脱颗粒相关的白细胞移出。这些数据表明，在人/SCID小鼠模型中，人肥大细胞脱颗粒会引发皮肤中的细胞炎症。在该模型中，用抗E选择素抗体显著抑制早期白细胞浸润的能力支持了这一分子在肥大细胞诱导的炎症中起重要作用的假说。
