Opioid Peptides Modulate the Organization of Vimentin Filaments, Phagocytic Activity, and Expression of Surface Molecules in Monocytes

Abstract

It is theorized that intermediate filaments are important in the modulation of membrane activity and cell motility; however, their functions are unknown. The assembly and organization of these filaments are under hormonal regulation. We investigated in human monocytes the in vitro effects of Met-enkephalin, Leu-enkephalin, and beta-endorphin on the expression of immunoreactive cytoskeletal vimentin filaments. We simultaneously examined their effect on the phagocytosis of Candida albicans and on the membrane display of surface molecules. The three opioid peptides markedly reduced the expression of vimentin filaments, the phagocytic activity, and the display of HLA-DR molecules at concentrations of 10(-6), 10(-8), and 10(-10) M. On the other hand, the intravenous administration of fentanyl, a synthetic opiate agonist, to patients undergoing surgery induced similar changes in monocytes. In other experiments, 10(-8) M beta-endorphin also decreased the expression of CR3 but did not influence the display of CD13, a surface protein of unknown function. Expression of vimentin filaments correlated directly with the display of HLA-DR antigens and CR3 and with the phagocytic activity. The results of this paper indicate that opiates and opioids, neuropeptides known to be released during stress, can directly depress several monocyte functions. Furthermore, from these data it may be speculated that intermediate filaments may regulate the membrane expression of some surface molecules and the phagocytic process.

Profiling Changes in Gene Expression during Differentiation and Maturation of Monocyte-derived Dendritic Cells Using Both Oligonucleotide Microarrays and Proteomics

“…Expression of secreted proteins involved in cell motility, autotaxin-t and semaphorin E, reported to play a role in axon guidance in the nervous system (26), was up-regulated. Up-regulation of the cytoskeleton-related proteins, the macrophage capping protein, and vimentin, all involved in cell motility (27,28), were also observed during DC differentiation. Therefore, the concomitant decrease in expression of integrins and cell adhesion molecules, the increase in expression of genes involved in cell motility, and regulated expression of enzymes such as ␣ 1 -antitrypsin and macrophage metalloelastase (HME) likely have an effect on the enhanced migration properties of DCs compared with their precursors.…”

Central nervous system-immune system interactions: psychoneuroendocrinology of stress and its immune consequences

“…Indeed, the changes in natural killer cell activity can be mimicked by administering morphine intracranially; this can also be blocked with naltrexone (14). Endorphins and/or enkephalins have also been shown to prevent lymphokine release (gamma interferon) from lymphocytes during an immune reaction (41), prevent mitogenesis in lymphocytes stimulated with various mitogens (23), decrease antibody response to antigens (22), and dysregulate cytoskeletal organization, phagocytosis, and display of class II antigens in monocytes (42). Moreover, various opioids that react with each of the three types of opiate receptors have produced decreased lymphocyte mitogenesis as well as antibody formation (44).…”

Direct influence of morphine on the release of arachidonic acid and its metabolites

“…3). the opioid peptide modulation of other immune parameters [16,17] [20,21] that naloxone can influence some functions of the immune system unrelated to its opioid receptor antagonism.…”