Jones H, Paul W, Page C P
Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, 5 Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.
Br J Pharmacol. 2001 Aug;133(7):1181-9. doi: 10.1038/sj.bjp.0704172.
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 ((125)I-bovine serum albumin, BSA) and cells ((111)In-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.
过敏性炎症反应会导致多种疾病的症状,包括特应性皮炎、哮喘和鼻炎。阳离子蛋白从炎症细胞中释放出来,并且已知在疾病状态下其水平会升高。我们使用急性炎症的体内模型,研究了皮肤对抗原(链格孢菌,AT)和聚-L-赖氨酸(PLL,用作阳离子蛋白的范例)的反应特征。我们旨在比较阳离子多肽的炎症特征和过敏反应,并确定这些反应之间的异同。使用放射性标记的蛋白质((125)I-牛血清白蛋白,BSA)和细胞((111)In-中性粒细胞,PMN)比较皮内注射聚阳离子、PLL和抗原后的反应,以研究AT致敏兔皮肤中的血浆渗出(PE)和PMN积聚(PMNA)。PLL和抗原均导致PE和PMNA呈剂量相关增加。对PLL的PE(和PMNA)反应持续时间延长(长达3小时),对抗原的反应也是如此。这与对fMLP的PE反应形成对比,后者在45分钟时达到最大值。在免疫动物中,用秋水仙碱(1 mg kg(-1)静脉注射)处理后,对直接作用介质缓激肽(BK)的PE反应不受影响,而对中性粒细胞依赖性介质f-甲硫-亮-苯丙氨酸(fMLP)的PE反应则显著(P<0.01)降低。秋水仙碱显著(50、500(P<0.05);200(P<0.01)p.n.u.部位(-1))抑制抗原诱导的PE反应,但PLL诱导的反应未受到显著影响。我们得出结论,尽管PLL诱导的反应与抗原诱导的反应具有相似时程,但在反应之间观察到了一些差异,这表明尽管聚阳离子可能促成过敏反应,但这两种反应是由不同机制产生的。