Taylor M B, Zweiman B, Moskovitz A R, von Allmen C, Atkins P C
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6057.
J Allergy Clin Immunol. 1990 Nov;86(5):740-8. doi: 10.1016/s0091-6749(05)80178-2.
We found increased accumulation of neutrophils and their components, lactoferrin (Lf) and elastase, as well as platelet-activating factor (PAF) and leukotriene B4 (LTB4) at sites of ongoing human allergic reactions. To determine whether PAF or LTB4, could be the stimulus for in vivo Lf release, blood neutrophils of 17 subjects were incubated with PAF, LTB4, or the phorbol ester, phorbol myristate acetate (PMA), and the released Lf (ELISA assay) was compared with spontaneous release. Significantly increased Lf release was induced by PAF, 10(-5) to 10(-8) mol/L (p less than 0.002); LTB4, 10(-7) to 10(-8) mol/L (p less than 0.004); and PMA (0.05 micrograms/ml) in a dose-dependent reaction. Cytochalasin was not required for Lf secretion but did enhance such responses. PAF-induced Lf secretion was inhibited by the specific PAF antagonist, BN 52063. More Lf was released from neutrophils of atopic than from nonatopic subjects in response to PAF, 10(-6) mol/L (4.2 micrograms/ml +/- 0.2 versus 2.6 micrograms/ml +/- 0.2; p less than 0.001) but not to LTB4, PMA, or buffer (p, not significant). We conclude that (1) PAF and LTB4 released in vivo could stimulate local neutrophils to release Lf with possible pathogenic effects and (2) neutrophils of atopic subjects are more responsive to PAF than neutrophils of nonatopic subjects in this regard.
我们发现在人类正在发生的过敏反应部位,中性粒细胞及其成分乳铁蛋白(Lf)和弹性蛋白酶、血小板活化因子(PAF)以及白三烯B4(LTB4)的积聚增加。为了确定PAF或LTB4是否可能是体内Lf释放的刺激物,将17名受试者的血液中性粒细胞与PAF、LTB4或佛波酯十四酰佛波醇乙酯(PMA)一起孵育,并将释放的Lf(酶联免疫吸附测定)与自发释放进行比较。PAF(10^(-5)至10^(-8) mol/L)可诱导Lf释放显著增加(p<0.002);LTB4(10^(-7)至10^(-8) mol/L)(p<0.004);以及PMA(0.05微克/毫升)呈剂量依赖性反应。Lf分泌不需要细胞松弛素,但细胞松弛素可增强这种反应。PAF诱导的Lf分泌被特异性PAF拮抗剂BN 52063抑制。在对10^(-6) mol/L的PAF反应中,特应性受试者的中性粒细胞释放的Lf比非特应性受试者更多(4.2微克/毫升±0.2对2.6微克/毫升±0.2;p<0.001),但对LTB4、PMA或缓冲液的反应则无差异(p无显著性)。我们得出结论:(1)体内释放的PAF和LTB4可刺激局部中性粒细胞释放Lf,可能具有致病作用;(2)在这方面,特应性受试者的中性粒细胞比非特应性受试者的中性粒细胞对PAF更敏感。