Malo P E, Wasserman M A, Pfeiffer D F
Prostaglandins. 1987 Feb;33(2):209-25. doi: 10.1016/0090-6980(87)90007-4.
The effect of platelet activating factor (PAF), a potent lipid mediator of inflammation, was examined in the induction of airway hyperreactivity to known mediators of anaphylaxis. Concentration-dependent contractions of the isolated guinea-pig trachea to PAF (10(-7)-10(-5) M) were produced and an EC50 value was found to be 7.5 X 10(-7) M. Pretreatment for 30 min with a known PAF inhibitor, CV-3988 (10(-5) or 10(-4) M), produced significant inhibition of PAF contractions; however, at 10(-6) M, CV-3988 had no effect. In the presence of meclofenamic acid (10(-6) M), the concentration-response curve to PAF was shifted significantly upward and to the left. This potentiation could be reversed by pretreating the tissues with the peptidoleukotriene antagonists, FPL 55712 or SK&F 102922 (10(-5) M). Pretreatment with PAF concentrations having essentially no intrinsic activity (10(-8), 10(-7)) significantly enhanced the contraction of guinea-pig trachea to various concentrations of LTD4 and to certain concentrations of a thromboxane mimic (U-46619). Pretreatment with lyso-PAF failed to potentiate the LTD4 response, while pretreatment with CV-3988 reverse the potentiation by PAF of the lower concentrations of LTD4. However, PAF failed to enhance contractions (with or without the presence of meclofenamic acid) to acetylcholine, histamine, PGD2 or LTC4 (in the presence of serine borate). These results indicate a possible role for PAF as a mediator of airway hyperreactivity.
研究了血小板活化因子（PAF）这一强效炎症脂质介质在诱导气道对已知过敏反应介质产生高反应性中的作用。分离的豚鼠气管对PAF（10^(-7)-10^(-5)M）产生浓度依赖性收缩，发现其半数有效浓度（EC50）值为7.5×10^(-7)M。用已知的PAF抑制剂CV-3988（10^(-5)或10^(-4)M）预处理30分钟，可显著抑制PAF引起的收缩；然而，在10^(-6)M时，CV-3988没有作用。在甲氯芬那酸（10^(-6)M）存在的情况下，PAF的浓度-反应曲线显著向上和向左移动。这种增强作用可通过用肽白三烯拮抗剂FPL 55712或SK&F 102922（10^(-5)M）预处理组织来逆转。用基本无内在活性的PAF浓度（10^(-8)、10^(-7)）预处理，可显著增强豚鼠气管对各种浓度白三烯D4（LTD4）和某些浓度血栓素类似物（U-46619）的收缩。溶血PAF预处理未能增强LTD4反应，而CV-3988预处理可逆转PAF对较低浓度LTD4的增强作用。然而，PAF未能增强（无论是否存在甲氯芬那酸）对乙酰胆碱、组胺、前列腺素D2（PGD2）或白三烯C4（LTC4，在丝氨酸硼酸盐存在的情况下）的收缩。这些结果表明PAF可能作为气道高反应性的介质发挥作用。
