DIFFERENTIAL RESPONSE TO A STRESS STIMULUS OF PROENKEPHALIN PEPTIDE CONTENT IN IMMUNE CELLS OF NAIVE AND CHRONICALLY STRESSED RATS

Proenkephalin peptides produced by endocrine and nervous tissues are i nvolved in stress-induced immunosuppression. However, the role of pept ides produced by immune cells remains unknown. The present study exami nes 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-enkepha lin in BMMC, while in TMC and SMC met-enkephalin represented 10% and 2 6% of total met-enkephalin-containing peptides, respectively. Naive ra ts receiving a stress stimulus showed a significant decrease of proenk ephalin derived peptides in BMMC, TMC and SMC. However, in chronically stressed rats that already showed basal low peptide levels, a new str ess stimulus produced a differential response in each immune tissue. T hat is, in BMMC peptide levels reached control rats values; in TMC rem ained unmodified; and in SMC, although precursors content increased, m et-enkephalin levels were even lower than those observed in acutely st ressed rats. Free synenkephalin content paralleled met-enkephalin chan ges in SMC of acutely and chronically stressed rats. The in vitro rele ase of met-enkephalin and free synenkephalin increased in SMC of stres sed rats. Met-enkephalin produced in SMC and partially processed proen kephalin peptides detected in BMMC, were only found in macrophages. Ho wever, met-enkephalin only appeared in bone marrow macrophages after a t least 4 h of cell culture. Altogether, these results suggest that a stress stimulus induced proenkephalin peptide release from immune tiss ue macrophages. The differential response observed in chronically stre ssed rats suggest an alternative activation of heterogeneous proenkeph alin-storing macrophage subpopulations.