Ying S, Meng Q, Taborda-Barata L, Kay A B
Imperial College School of Medicine, National Heart & Lung Institute, London, U.K.
Proc Assoc Am Physicians. 1997 Jan;109(1):42-50.
The allergen-induced cutaneous late-phase response serves as a model of allergic inflammation and is associated with infiltration of neutrophils, eosinophils, T cells, and macrophages. The mechanisms controlling the resolution of allergic inflammatory processes and the fate of infiltrating cells are uncertain. We observed that both the magnitude of the late-phase response and the numbers of infiltrating neutrophils and eosinophils peaked at 6 hr, persisted for 48 hr, but resolved completely by 7 days. In contrast, T-cell and macrophage numbers peaked between 24 and 72 hr after allergen challenge and persisted for up to 7 days. By using the techniques of terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine 5'-triphosphate (dUTP) nickend-labeling (TUNEL) and by combining TUNEL with immunohistochemistry, we tested the hypothesis that the resolution of the late-phase response is associated with apoptosis of neutrophils and eosinophils, with subsequent engulfment of apoptotic cells and apoptotic bodies by tissue macrophages. As the cutaneous late-phase response resolved, there was a progressive increase (peaking at 72 hr) in the total numbers of TUNEL-positive (TUNEL+) cells and in the numbers of macrophages that had engulfed apoptotic cells and bodies. The majority of TUNEL+ cells were identified as neutrophils and eosinophils. In contrast, very little apoptosis was associated with T cells or macrophages. These experiments represent a novel demonstration of cell type-specific apoptosis in vivo in human allergic inflammatory tissue and suggest that phagocytosis by macrophages of apoptotic neutrophils and eosinophils may be a mechanism that regulates resolution of the atopic allergic inflammatory response.
变应原诱导的皮肤迟发相反应是变应性炎症的一种模型，与中性粒细胞、嗜酸性粒细胞、T细胞和巨噬细胞的浸润有关。控制变应性炎症过程消退以及浸润细胞命运的机制尚不清楚。我们观察到，迟发相反应的强度以及浸润的中性粒细胞和嗜酸性粒细胞数量在6小时达到峰值，持续48小时，但在7天时完全消退。相比之下，T细胞和巨噬细胞数量在变应原激发后24至72小时达到峰值，并持续长达7天。通过使用末端脱氧核苷酸转移酶介导的生物素-脱氧尿苷5'-三磷酸（dUTP）缺口末端标记（TUNEL）技术，并将TUNEL与免疫组织化学相结合，我们检验了以下假设：迟发相反应的消退与中性粒细胞和嗜酸性粒细胞的凋亡有关，随后组织巨噬细胞吞噬凋亡细胞和凋亡小体。随着皮肤迟发相反应的消退，TUNEL阳性（TUNEL+）细胞总数以及吞噬凋亡细胞和凋亡小体的巨噬细胞数量逐渐增加（在72小时达到峰值）。大多数TUNEL+细胞被鉴定为中性粒细胞和嗜酸性粒细胞。相比之下，与T细胞或巨噬细胞相关的凋亡很少。这些实验首次证明了人类变应性炎症组织中体内细胞类型特异性凋亡，并表明巨噬细胞对凋亡中性粒细胞和嗜酸性粒细胞的吞噬作用可能是调节特应性变应性炎症反应消退的一种机制。
