Hellewell P G, Williams T J
J Immunol. 1986 Jul 1;137(1):302-7.
The properties of a novel platelet-activating factor (PAF) antagonist, L-652731, on oedema responses in rabbit skin induced by exogenous inflammatory mediators and by mediators generated endogenously in a reversed passive Arthus reaction have been investigated. Oedema responses in the skin were measured by using the local accumulation of i.v. injected 125I-albumin. The antagonist, mixed with mediators before intradermal injection, caused a dose-dependent suppression of oedema responses to PAF. In contrast, responses induced by other directly acting mediators (bradykinin and histamine) and responses induced by PMN leukocyte-dependent mediators (C5a des Arg, N-formyl-methionyl-leucyl-phenylalanine, and leukotriene B4) were not suppressed. Thus, a secondary release of PAF does not appear to be involved in mediating the actions of these agents. In a reversed passive Arthus reaction, intradermal injection of L-652731 together with antibody resulted in a significant inhibition of the oedema formation measured for 2 hr after i.v. antigen challenge. In contrast, oedema responses induced by intradermal injection of preformed immune complexes were not affected by the antagonist. These results suggest that the endogenous production of PAF, in close proximity to microvascular endothelial cells, appears to be an important step in the development of an Arthus reaction. The cellular source of PAF is unknown, but one possibility is the PMN leukocyte, which releases PAF during phagocytosis of immune complexes.
研究了新型血小板活化因子（PAF）拮抗剂L-652731对外源性炎症介质以及在反向被动Arthus反应中内源性产生的介质所诱导的兔皮肤水肿反应的作用。通过静脉注射125I-白蛋白的局部蓄积来测量皮肤中的水肿反应。在皮内注射前将拮抗剂与介质混合，可导致对PAF诱导的水肿反应产生剂量依赖性抑制。相比之下，由其他直接作用介质（缓激肽和组胺）诱导的反应以及由PMN白细胞依赖性介质（C5a des Arg、N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸和白三烯B4）诱导的反应未被抑制。因此，PAF的二次释放似乎不参与介导这些介质的作用。在反向被动Arthus反应中，皮内注射L-652731与抗体一起，可显著抑制静脉注射抗原激发后2小时测量的水肿形成。相比之下，皮内注射预先形成的免疫复合物诱导的水肿反应不受拮抗剂影响。这些结果表明，在微血管内皮细胞附近内源性产生PAF似乎是Arthus反应发生过程中的一个重要步骤。PAF的细胞来源尚不清楚，但一种可能性是PMN白细胞，其在吞噬免疫复合物过程中释放PAF。
