Whyte A, Licence S T, Robinson M K, van der Lienden K
Department of Immunology, Babraham Institute, Cambridge, United Kingdom.
Lab Invest. 1996 Sep;75(3):439-49.
Kinetic and phenotypic heterogeneity in leukocyte subsets and adhesion-molecule expression is characteristic of many inflammatory conditions. We have studied the effect of various cytokines and inflammatory agonists on the type of leukocyte present and the adhesion molecules expressed in acute lesions (up to 3 days old) in porcine skin by immunohistology. Four major histocompatability complex-homozygous inbred pigs received replicate intradermal injections of IL-1 alpha, TNF-alpha, PMA, or PHA. Injections were timed so that lesions were obtained at 2, 4, 9, and 24 hours. Another two animals were studied at time points up to 72 hours. Leukocyte subsets and endothelial adhesion molecules were visualized on cryosections by use of monoclonal antibodies and alkaline phosphatase immunohistologic techniques. Substantial heterogeneity in leukocyte phenotypes was observed with all agonists, with lymphocyte subsets showing the greatest variation. Thus, CD2+ and gamma delta TcR+ (Null) T lymphocytes were present in all lesions, but to a varying extent such that few T cells were seen after PMA injection, approximately equal proportions of each after TNF-alpha, but substantially more gamma delta TcR+ (Null) lymphocytes were noted after PHA administration. Endothelial adhesion molecules were also variously affected, with E-selectin (CD62E) being transiently up-regulated by IL-1 alpha but CD62E showed early and sustained expression after TNF-alpha and PHA administration. The E-selectin ligand was demonstrated on infiltrating gamma delta TcR+ lymphocytes by use of a recombinant porcine E-selectin. The L-selectin ligand, identified by the mAb MECA-79, was only observed in late acute sites (< 24 hours) of TNF-alpha and PHA. Endothelial expression of class II major histocompatability complex was also variously up-regulated by all agonists. The results underline the heterogeneity of leukocyte phenotypes and endothelial adhesion molecule expression in acute cutaneous lesions dependent upon the nature of the inflammatory agonist and indicate an association between endothelial E-selectin and the presence of a gamma delta TcR+ (Null) T lymphocyte subset.
白细胞亚群的动力学和表型异质性以及黏附分子表达是许多炎症状态的特征。我们通过免疫组织学研究了各种细胞因子和炎性激动剂对猪皮肤急性损伤（3天以内）中存在的白细胞类型和表达的黏附分子的影响。4只主要组织相容性复合体纯合的近交系猪接受了白细胞介素-1α、肿瘤坏死因子-α、佛波酯或植物血凝素的重复皮内注射。注射时间安排使得在2、4、9和24小时获得损伤样本。另外两只动物在长达72小时的时间点进行研究。通过使用单克隆抗体和碱性磷酸酶免疫组织学技术，在冷冻切片上观察白细胞亚群和内皮黏附分子。所有激动剂均观察到白细胞表型存在显著异质性，淋巴细胞亚群变化最大。因此，CD2⁺和γδT细胞受体⁺（空）T淋巴细胞存在于所有损伤中，但程度不同，以至于在佛波酯注射后几乎看不到T细胞，肿瘤坏死因子-α注射后两者比例大致相等，但在植物血凝素给药后观察到γδT细胞受体⁺（空）淋巴细胞明显更多。内皮黏附分子也受到不同影响，E-选择素（CD62E）被白细胞介素-1α短暂上调，但肿瘤坏死因子-α和植物血凝素给药后CD62E表现出早期且持续的表达。通过使用重组猪E-选择素，在浸润的γδT细胞受体⁺淋巴细胞上证实了E-选择素配体。由单克隆抗体MECA-79识别的L-选择素配体仅在肿瘤坏死因子-α和植物血凝素的急性晚期部位（<24小时）观察到。所有激动剂也不同程度地上调了II类主要组织相容性复合体的内皮表达。结果强调了急性皮肤损伤中白细胞表型和内皮黏附分子表达的异质性取决于炎性激动剂的性质，并表明内皮E-选择素与γδT细胞受体⁺（空）T淋巴细胞亚群的存在之间存在关联。
