Crouch S P, Crocker I P, Fletcher J
Medical Research Centre, City Hospital NHS Trust, Nottingham, United Kingdom.
J Immunol. 1995 Dec 1;155(11):5436-43.
Pregnancy exerts suppressive effects on a number of chronic inflammatory conditions, particularly rheumatoid arthritis. We isolated peripheral blood polymorphonuclear leukocytes (PMN) from pregnant women at 30 to 34 wk (n = 34) and showed significant reductions in respiratory burst activity compared with nonpregnant controls (n = 34), as determined by lucigenin-enhanced chemiluminescence (LUCL). Responses to FMLP were reduced by 54% (p = 0.0046) and to zymosan-activated serum (ZAS) by 69% (p = 0.0043). Following LUCL responses to these agonists in women throughout the course of their pregnancy (n = 7) revealed significantly reduced responses by the second and third trimesters (p < 0.005). Intracellular H2O2 production in PMN at 30 to 34 wk gestation was significantly reduced (p = 0.0454) in response to FMLP, compared with the nonpregnant controls. Investigation of adhesion molecule expression revealed no differences in CD11b or CD18. However, loss of CD62L from the PMN surface in response to FMLP and ZAS was significantly reduced at 30 to 34 wk, as compared with controls (FMLP, p = 0.049; ZAS, p = 0.01; n = 34). There were no significant differences in cell surface formyl peptide receptor expression, although there were statistical differences in LUCL responses to all concentrations of FMLP used (p < 0.05). Incubating PMN with TNF, IL-8, and granulocyte-macrophage CSF increased formyl peptide receptor expression but revealed no differences between the two groups. Priming of pregnancy PMN with the same cytokines gave significantly reduced LUCL when cells were subsequently stimulated with FMLP (p < 0.05; n = 6). Our results show a reduction in PMN NADPH-oxidase activity during pregnancy and may offer a partial explanation for the remission of symptoms observed in rheumatoid arthritis.
妊娠对多种慢性炎症性疾病具有抑制作用,尤其是类风湿性关节炎。我们从30至34周的孕妇中分离出外周血多形核白细胞(PMN)(n = 34),并通过光泽精增强化学发光法(LUCL)测定发现,与非孕对照组(n = 34)相比,其呼吸爆发活性显著降低。对FMLP的反应降低了54%(p = 0.0046),对酵母聚糖激活血清(ZAS)的反应降低了69%(p = 0.0043)。在整个孕期(n = 7)对这些激动剂进行LUCL反应后发现,孕中期和孕晚期的反应显著降低(p < 0.005)。与非孕对照组相比,妊娠30至34周时PMN对FMLP的反应中细胞内H2O2生成显著降低(p = 0.0454)。对黏附分子表达的研究显示,CD11b或CD18没有差异。然而,与对照组相比,妊娠30至34周时PMN表面因FMLP和ZAS导致的CD62L丢失显著减少(FMLP,p = 0.049;ZAS,p = 0.01;n = 34)。细胞表面甲酰肽受体表达没有显著差异,尽管对所有使用浓度的FMLP的LUCL反应存在统计学差异(p < 0.05)。用TNF、IL - 8和粒细胞 - 巨噬细胞集落刺激因子孵育PMN可增加甲酰肽受体表达,但两组之间没有差异。当随后用FMLP刺激细胞时,用相同细胞因子预处理妊娠PMN会使LUCL显著降低(p < 0.05;n = 6)。我们的结果表明妊娠期间PMN的NADPH氧化酶活性降低,这可能为类风湿性关节炎中观察到的症状缓解提供部分解释。