Investigation of the functional role played by the chemokine monocyte chemoattractant protein-1 in interleukin-1-induced murine peritonitis
Investigation of the functional role played by the chemokine monocyte chemoattractant protein-1 in interleukin-1-induced murine peritonitis
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DOI：
10.1038/sj.bjp.0702071
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发表时间：
1998-09-01
影响因子：
7.3
通讯作者：
Perretti, M
中科院分区：
文献类型：
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作者：
Ajuebor, MN;Gibbs, L;Perretti, M
1腹膜内(I.P.)注射小鼠重组IL-1β(mrIL-1β)后，灌洗液中小鼠单核细胞趋化蛋白-1(mMCP-1)的分泌呈剂量依赖性(0.5-50 ng)和时间依赖性(0.5-2 h)。单核细胞趋化蛋白-1mRNA。逆转录聚合酶链式反应(RT-PCR)检测到MCP-1的表达。2联合应用IL-1受体拮抗剂(10mU/g)可使MCP-1水平下降90%以上(n=6，P<0.05)。相比之下，与IL-1受体I型亲和力低的IL-1突变体，称为YIL-1B Delta 4(50 Ng)，仅产生适度的趋化因子释放。地塞米松(DEX)对小鼠的治疗作用(相当于1 mg kg(-1)S.C.)减少mrIL-1β诱导的mMCP-1基因表达(明显完全抑制)和灌洗液中蛋白释放(类似于减少40%；n=10；P<；0.05)。巨噬细胞和肥大细胞数量的急剧减少并没有改变灌洗液中mMCP-1的水平。3注射mrIL-1β可使中性粒细胞聚集到腹膜腔(4h达到最大值，每只小鼠有1.42+/-0.15×10h的细胞)。注射抗mMCP-1的特异性多克隆抗体可使这一过程减少50%以上(n=6；P<；0.05)。总之，我们研究了体内注射mrIL-1β后导致CC趋化因子mMCP-1特异性释放的机制。
1 Intraperitoneal (i.p.) injection of murine recombinant IL-I beta (mrIL-1 beta) produced a dose-dependent (0.5-50 ng) and time-related (0.5-2 h) secretion of murine monocyte chemoattractant protein-1 (mMCP-1; 3-4 ng per cavity) in the lavage fluids. MCP-1 mRNA. could also be detected in the cell pellets by reverse transcriptase-polymerase chain reaction (RT-PCR).2 MCP-1 levels were reduced by more than 90% by co-administration of IL-1 receptor antagonist (10 mu g) (n = 6, P < 0.05). In contrast, an IL-1 mutant with low affinity for IL-1 receptor type I, termed yIL-1B Delta 4 (50 ng), produced only a modest release of the chemokine. Treatment of mice with dexamethasone (DEX) (similar to 1 mg kg(-1) s.c.) reduced mrIL-1 beta-induced mMCP-1 gene expression (apparent total inhibition) and protein release in the lavage fluids (similar to 40% reduction; n = 10; P < 0.05). Drastic reductions in the numbers of residential macrophages or mast cells did not modify the levels of mMCP-1 recovered in the lavage fluids.3 Injection of mrIL-1 beta produced neutrophil accumulation into the peritoneal cavities (maximal at 4 h with 1.42 +/- 0.15 x 10 h cells per mouse). Go-injection of a specific polyclonal antibody against mMCP-1 reduced this process by more than 50% (n = 6; P < 0.05). In conclusion, we studied the mechanisms leading to the specific release of the CC chemokine mMCP-1 after in vivo administration of mrIL-1 beta.