Bouchelouche P N, Berild D, Nielsen O H, Elmgreen J, Poulsen H S
Department of Clinical Chemistry, Herlev Hospital, University of Copenhagen, Denmark.
Eur J Gastroenterol Hepatol. 1995 Apr;7(4):349-56.
To investigate the leukotriene B4 (LTB4) signal transducing mechanism in polymorphonuclear neutrophils (PMNs) from patients with Crohn's disease.
Cytosolic free calcium ([Ca2+]i), inositol (1,4,5)-trisphosphate [(1,4,5)-IP3] chemotaxis, LTB4 receptor number and affinity were investigated in peripheral PMNs from 11 patients with Crohn's disease and 11 healthy controls.
There was a slight reduction (P = 0.31) in the number of LTB4 receptor sites per cell expressed on PMNs (mean Bmax 931) from nine of the 11 patients studied compared with the healthy controls (mean Bmax 1095). LTB4-mediated (1,4,5)-IP3 formation and the increase in [Ca2+]i were markedly decreased in PMNs from the 11 patients with Crohn's disease [(1,4,5)-IP3, mean +/- SEM 12 +/- 0.84 and 27.4 +/- 1.4 pmol/l/tube for patients and controls, respectively; [Ca2+]i, mean +/- SEM 295 +/- 2.75 and 598 +/- 4.7 nmol/l for patients and controls, respectively]. The decrease in calcium might be related to the decrease in Bmax (P < 0.05). Ionomycin, a calcium ionophore which bypasses the initial steps of LTB4 receptor activation, showed only a minor difference in peak [Ca2+]i between PMNs from patients and controls. LTB4-directed chemotaxis showed that the sensitivity to suboptimal concentrations of LTB4 (1.0 nmol/l) was significantly depressed in PMNs from patients (P < 0.05).
Peripheral PMNs from patients with Crohn's disease had a small deficit in the expression of LTB4 receptors. This deficiency was paralleled by marked alterations in cellular signalling. Whether these results are specific to Crohn's disease or simply result from the exposure of circulating PMNs to elevated levels of LTB4 remains to be established.
研究克罗恩病患者多形核中性粒细胞（PMN）中白三烯B4（LTB4）信号转导机制。
对11例克罗恩病患者及11名健康对照者外周血PMN中的细胞内游离钙（[Ca2+]i）、肌醇（1,4,5）-三磷酸（[1,4,5]-IP3）趋化作用、LTB4受体数量及亲和力进行研究。
与健康对照者（平均最大结合量1095）相比，11例研究患者中有9例患者PMN上每个细胞表达的LTB4受体位点数量略有减少（P = 0.31）（平均最大结合量931）。11例克罗恩病患者的PMN中，LTB4介导的[1,4,5]-IP3形成及[Ca2+]i增加明显降低（[1,4,5]-IP3，患者组和对照组分别为平均±标准误12±0.84和27.4±1.4 pmol/l/管；[Ca2+]i，患者组和对照组分别为平均±标准误295±2.75和598±4.7 nmol/l）。钙的减少可能与最大结合量的降低有关（P < 0.05）。离子霉素是一种绕过LTB4受体激活初始步骤的钙离子载体，患者和对照者PMN之间的[Ca2+]i峰值仅显示出微小差异。LTB4诱导的趋化作用表明，患者PMN对次优浓度LTB4（1.0 nmol/l）的敏感性显著降低（P < 0.05）。
克罗恩病患者外周血PMN中LTB4受体表达略有不足。这种缺陷与细胞信号传导的明显改变平行。这些结果是克罗恩病所特有的，还是仅仅由于循环PMN暴露于高水平LTB4所致，仍有待确定。
