肥大细胞在吗啡介导的小鼠酵母聚糖诱导的腹膜炎损伤中的关键作用。

Critical role of mast cells in morphine-mediated impairment of zymosan-induced peritonitis in mice.

作者信息

Kolaczkowska E, Seljelid R, Plytycz B

机构信息

Department of Experimental Pathology, Institute of Medical Biology, University of Tromsø, Norway.

出版信息

Inflamm Res. 2001 Aug;50(8):415-21. doi: 10.1007/PL00000264.

DOI:10.1007/PL00000264

PMID:11556522

Abstract

OBJECTIVE AND DESIGN

Zymosan-induced peritoneal inflammation is significantly inhibited in mice injected with an irritant supplemented with morphine. The aim of the present study was to examine the putative mast cell involvement in this inhibition.

SUBJECTS

Peritonitis was induced in WBB6FI mice (genetically mast cell-deficient W/Wv and their control littermaters +/+) and in Balb/c mice, with normal mast cells (MC) and mast cell-depleted (MCx) by pretreatment with compound 48/80. Bone marrow leukocytes from intact Balb/c mice were tested for their sensitivity to chemoattractants after in vitro incubation with morphine (10(-6) M), with or without preincubation with naltrexone (10(-8) M). Control cells were incubated in medium only.

TREATMENT

Peritonitis was induced by i.p. injection of either zymosan only (Z, 2 mg/ml) or zymosan supplemented with morphine (ZM, M: 20 mg/kg), without or with pretreatment with naltrexone (NZM, N: 5 mg/kg).

METHODS

Thirty minutes after induction of peritonitis, the histamine levels (ELISA) and vascular permeability (Evans blue leakage) were measured. At 6 h, the number of exudatory leukocytes (haemocytometer) and chemotaxis/chemoattractant level (48-well chemotactic chamber) were estimated.

RESULTS

(1) At 6 h of peritonitis, the number of exudatory leukocytes and levels of plasma chemoattractants were significantly lower in animals injected with zymosan supplemented with morphine (ZM) than in Z and NZM groups of WBB6F1 and Balb/c mice, but only in those with normal mast cells, and not in their mast cell-deficient/depleted counterparts. (2) In contrast, at 30 minutes, vascular permeability and histamine levels were higher in ZM than in Z group of mice with normal mast cells (MC), but not in those depleted of mast cells (MCx). (3) In vitro preincubation of leukocytes with morphine inhibited their migratory activity only towards peritoneal fluid from zymosan-treated MC mice but not from their MCx counterparts.

CONCLUSIONS

Mast cell-derived factors are involved in morphine-mediated impairment of zymosan-induced peritonitis in mice.

摘要

目的与设计

在用补充了吗啡的刺激物注射的小鼠中，酵母聚糖诱导的腹膜炎受到显著抑制。本研究的目的是检验肥大细胞在这种抑制中可能的参与情况。

对象

在WBB6F1小鼠（基因缺陷型肥大细胞W/Wv及其对照同窝小鼠+/+）以及Balb/c小鼠中诱导腹膜炎，Balb/c小鼠具有正常肥大细胞（MC），且通过用化合物48/80预处理使其肥大细胞耗竭（MCx）。将完整Balb/c小鼠的骨髓白细胞在体外用吗啡（10⁻⁶ M）孵育，无论是否预先用纳曲酮（10⁻⁸ M）孵育，然后检测其对趋化因子的敏感性。对照细胞仅在培养基中孵育。

处理

通过腹腔注射单独的酵母聚糖（Z，2 mg/ml）或补充了吗啡的酵母聚糖（ZM，M：20 mg/kg）诱导腹膜炎，无论是否预先用纳曲酮（NZM，N：5 mg/kg）处理。

方法

在诱导腹膜炎30分钟后，测量组胺水平（酶联免疫吸附测定）和血管通透性（伊文思蓝渗漏）。在6小时时，估计渗出白细胞数量（血细胞计数器）和趋化性/趋化因子水平（48孔趋化室）。

结果

（1）在腹膜炎6小时时，注射补充了吗啡的酵母聚糖（ZM）的动物中，渗出白细胞数量和血浆趋化因子水平显著低于WBB6F1和Balb/c小鼠的Z组和NZM组，但仅在具有正常肥大细胞的动物中如此，而在其肥大细胞缺陷/耗竭的对应动物中并非如此。（2）相反，在30分钟时，具有正常肥大细胞（MC）的小鼠中，ZM组的血管通透性和组胺水平高于Z组，但在肥大细胞耗竭（MCx）的小鼠中并非如此。（3）白细胞在体外用吗啡预先孵育仅抑制其对来自酵母聚糖处理的MC小鼠而非MCx对应小鼠的腹膜液的迁移活性。