Saravia F, Padros M R, Ase A, Aloyz R, Duran S, Vindrola O
Instituto de Fisiologia, Laboratorio de Bioquimica, Universidad Autonoma de Puebla, Mexico.
Neuropeptides. 1998 Aug;32(4):351-9. doi: 10.1016/s0143-4179(98)90058-0.
Proenkephalin peptides produced by endocrine and nervous tissues are involved in stress-induced immunosuppression. However, the role of peptides produced by immune cells remains unknown. The present study examines the effect of acute and chronic foot-shock stress on proenkephalin peptide content in bone marrow (BMMC), thymus (TMC), and spleen (SMC) rat mononuclear cells. Proenkephalin was not processed to met-enkephalin in BMMC, while in TMC and SMC met-enkephalin represented 10% and 26% of total met-enkephalin-containing peptides, respectively. Naive rats receiving a stress stimulus showed a significant decrease of proenkephalin derived peptides in BMMC, TMC and SMC. However, in chronically stressed rats that already showed basal low peptide levels, a new stress stimulus produced a differential response in each immune tissue. That is, in BMMC peptide levels reached control rats values; in TMC remained unmodified; and in SMC, although precursors content increased, met-enkephalin levels were even lower than those observed in acutely stressed rats. Free synenkephalin content paralleled met-enkephalin changes in SMC of acutely and chronically stressed rats. The in vitro release of met-enkephalin and free synenkephalin increased in SMC of stressed rats. Met-enkephalin produced in SMC and partially processed proenkephalin peptides detected in BMMC, were only found in macrophages. However, met-enkephalin only appeared in bone marrow macrophages after at least 4 h of cell culture. Altogether, these results suggest that a stress stimulus induced proenkephalin peptide release from immune tissue macrophages. The differential response observed in chronically stressed rats suggest an alternative activation of heterogeneous proenkephalin-storing macrophage subpopulations.
内分泌和神经组织产生的前脑啡肽原肽参与应激诱导的免疫抑制。然而，免疫细胞产生的肽的作用仍不清楚。本研究检测了急性和慢性足部电击应激对大鼠骨髓（BMMC）、胸腺（TMC）和脾脏（SMC）单核细胞中前脑啡肽原肽含量的影响。在BMMC中，前脑啡肽原未加工成甲硫氨酸脑啡肽，而在TMC和SMC中，甲硫氨酸脑啡肽分别占含甲硫氨酸脑啡肽肽总量的10%和26%。接受应激刺激的未处理大鼠，其BMMC、TMC和SMC中前脑啡肽衍生肽显著减少。然而，在已经表现出基础肽水平较低的慢性应激大鼠中，新的应激刺激在每个免疫组织中产生了不同的反应。也就是说，BMMC中的肽水平达到了对照大鼠的值；TMC中的肽水平未改变；而在SMC中，尽管前体含量增加，但甲硫氨酸脑啡肽水平甚至低于急性应激大鼠中观察到的水平。游离的突触脑啡肽含量与急性和慢性应激大鼠SMC中甲硫氨酸脑啡肽的变化平行。应激大鼠SMC中甲硫氨酸脑啡肽和游离突触脑啡肽的体外释放增加。在SMC中产生的甲硫氨酸脑啡肽和在BMMC中检测到的部分加工的前脑啡肽原肽，仅在巨噬细胞中发现。然而，甲硫氨酸脑啡肽仅在细胞培养至少4小时后出现在骨髓巨噬细胞中。总之，这些结果表明应激刺激诱导免疫组织巨噬细胞释放前脑啡肽原肽。在慢性应激大鼠中观察到的不同反应表明，储存前脑啡肽的巨噬细胞亚群存在交替激活。
