A comparison of allergen and polycation induced cutaneous responses in the rabbit
作者:Helen Jones、William Paul、Clive P Page
DOI:10.1038/sj.bjp.0704172
日期:2001.8
Allergic inflammatory responses contribute to the symptoms of a number of diseases including atopic dermatitis, asthma and rhinitis. Cationic proteins are released from inflammatory cells and levels are known to be raised in disease states.
Using an in vivo model of acute inflammation, we investigated the characteristics of cutaneous responses to antigen (Alternaria tenuis, AT) and poly‐L‐lysine (PLL, used as a paradigm for cationic proteins). We aimed to compare the inflammatory profile of cationic polypeptides and the allergic response and to identify similarities and differences between these responses.
Responses to intradermal injection of the polycation, PLL and antigen were compared using radiolabelled protein (125I‐bovine serum albumin, BSA) and cells (111In‐neutrophils, PMN) to study plasma exudation (PE) and PMN accumulation (PMNA) in the skin of AT sensitized rabbits.
Both PLL and antigen caused dose‐related increases in PE and PMNA. PE (and PMNA) responses to PLL were prolonged (up to 3 h), as were those to antigen. This is in contrast to PE responses to fMLP which were maximal at 45 min.
In immunized animals, treated with colchicine (1 mg kg−1 i.v.), PE responses to the directly acting mediator, bradykinin (BK), were not affected, whereas PE responses to the neutrophil dependent mediator, f‐met‐leu‐phe (fMLP), were significantly (P<0.01) reduced. Antigen‐induced PE responses were significantly (50, 500 (P<0.05); 200 (P<0.01) p.n.u. site−1) inhibited by colchicine, but PLL‐induced responses were not significantly affected.
We conclude that although PLL‐induced responses had a similar time course to those of antigen, some differences were observed between responses, which indicate that although polycations may contribute to allergic responses, these two responses are produced by distinct mechanisms.
British Journal of Pharmacology (2001) 133, 1181–1189; doi:10.1038/sj.bjp.0704172
过敏性炎症反应会导致多种疾病的发生,如异位性皮炎、哮喘和鼻炎。阳离子蛋白由炎性细胞释放,已知其在疾病状态下水平升高。
我们采用急性炎症的体内模型,研究抗原(*Alternaria tenuis*,AT)和多聚-L-赖氨酸(PLL,用于模拟阳离子蛋白)引起的皮肤反应特征。旨在比较阳离子多肽的炎症特征与过敏反应,并识别其异同点。
通过放射性标记蛋白质(125I-牛血清白蛋白,BSA)和细胞(111In-中性粒细胞,PMN),研究多聚阳离子PLL和抗原皮内注射在AT致敏兔皮肤中的血浆渗出(PE)和PMN积聚(PMNA)。
无论是PLL还是抗原,均导致剂量相关性的PE和PMNA增加。PLL引起的PE(及PMNA)反应持续时间较长(达3小时),抗原诱导的反应同样持续较久。这与fMLP诱导的PE反应不同,后者在45分钟时达到峰值。
处理免疫动物给予秋水仙素(1 mg kg⁻¹,iv),对直接作用介质缓激肽(BK)诱导的PE反应无影响,但显著减少了依赖中性粒细胞的介质f-met-leu-phe(fMLP)引起的PE反应(P < 0.01)。抗原诱导的PE反应被秋水仙素显著抑制(50, 500 p.n.u. site⁻¹,P < 0.05; 200 p.n.u. site⁻¹,P < 0.01),而PLL引起的反应未见显著变化。
结论:尽管PLL与抗原引起的反应时间进程相似,但两者仍存在差异,提示虽然多聚阳离子可能参与过敏反应,但两者由不同的机制介导。