Spoelstra F M, Hovenga H, Noordhoek J A, Postma D S, Kauffman H F
Departments of Allergology and Pulmonology, University Hospital Groningen, Groningen, The Netherlands.
Am J Respir Crit Care Med. 1998 Sep;158(3):769-77. doi: 10.1164/ajrccm.158.3.9712143.
Eosinophilic airway infiltration is a central feature in asthma. Eosinophils recovered from bronchoalveolar fluid show an activated phenotype, e.g., increased CD11b and decreased L-selectin expression. We investigated whether lung fibroblasts are able to activate eosinophils in vitro, and if so, which activating factor is most important. CD11b and L-selectin expression of isolated peripheral blood eosinophils were measured by flow cytometry after coculture with normal lung fibroblasts or their conditioned medium. We found that eosinophil CD11b expression increased (154% and 210%, p < 0.05) and L-selectin expression decreased (59% and 35.5%, p < 0.05) on eosinophils compared with baseline (100%) after 4 and 24 h of coculture with interleukin-1-beta (IL-1beta)-stimulated fibroblasts, respectively. Conditioned medium of stimulated fibroblasts also increased CD11b expression, but to a smaller extent (p < 0.05). L-selectin expression of eosinophils in cocultures was not different from that of eosinophils in conditioned medium. Only anti-granulocyte/macrophage colony-stimulating factor (anti-GM-CSF) reduced the activation of eosinophils in conditioned medium to almost basal levels (p < 0.05). An increase in CD11b expression is mediated by cytokines as well as direct cell contact, whereas a decrease in L-selectin expression is only mediated by cytokines. GM-CSF released by fibroblasts is an important factor in the modulation of both CD11b and L-selectin expression. These results show that lung fibroblasts can activate eosinophils by both adhesive interactions and by soluble factors.
嗜酸性气道浸润是哮喘的核心特征。从支气管肺泡灌洗液中回收的嗜酸性粒细胞表现出活化表型，例如CD11b增加和L-选择素表达降低。我们研究了肺成纤维细胞是否能够在体外激活嗜酸性粒细胞，如果可以，哪种激活因子最为重要。将分离的外周血嗜酸性粒细胞与正常肺成纤维细胞或其条件培养基共培养后，通过流式细胞术测量嗜酸性粒细胞CD11b和L-选择素的表达。我们发现，与白细胞介素-1-β（IL-1β）刺激的成纤维细胞共培养4小时和24小时后，嗜酸性粒细胞的CD11b表达分别增加（154%和210%，p<0.05），L-选择素表达降低（59%和35.5%，p<0.05），与基线（100%）相比。刺激的成纤维细胞的条件培养基也增加了CD11b表达，但程度较小（p<0.05）。共培养中嗜酸性粒细胞的L-选择素表达与条件培养基中嗜酸性粒细胞的L-选择素表达没有差异。只有抗粒细胞/巨噬细胞集落刺激因子（抗GM-CSF）将条件培养基中嗜酸性粒细胞的活化降低到几乎基础水平（p<0.05）。CD11b表达的增加由细胞因子以及直接细胞接触介导，而L-选择素表达的降低仅由细胞因子介导。成纤维细胞释放的GM-CSF是调节CD11b和L-选择素表达的重要因素。这些结果表明，肺成纤维细胞可以通过黏附相互作用和可溶性因子激活嗜酸性粒细胞。
