Enkephalins stimulate leukemia cell migration and surface expression of CD9.

Abstract

Opioid peptides have been implicated in the regulation of tumor growth and biology; however, little attention has been given to the mechanisms that are involved. In this study we show that physiological concentrations of the endogenous opioid neuropeptide methionine-enkephalin (MET-ENK) and the synthetic enkephalins D-Ala2,Me-Phe4,Gly(ol)' and D-Ala2,D-Leu5 are stimulants for the in vitro migration of pre-B acute lymphoblastoid leukemia (ALL) cells. Activation of the human pre-B ALL cell lines NALM 6 and LAZ 221 with MET-ENK resulted in both an increase in their migration and an augmentation in the surface expression of the leukemia cell marker CD9. The opiate receptor antagonist naloxone reversed these enkephalin-induced effects on the leukemia cells. When the pre-B ALL cells were preincubated with an anti-CD9 mAb before challenge with MET-ENK their migration to the enkephalin was markedly reduced. These studies show that endogenous and synthetic opioid peptides are stimulants for pre-B ALL cell migration and suggest that CD9 is important in the regulation of leukemia cell motility. (J. Clin. Invest. 1995. 96:1366-1374

Aminopeptidase B from the rat testis is a bifunctional enzyme structurally related to leukotriene-A4 hydrolase

“…The broad pH dependence of the enzyme (18) and its ubiquitous presence (19) argue in favor of its adaptability to various cellular subcompartments and its implication in a broad spectrum of physiological phenomena, including processing, but also inflammatory processes in which some potential peptide substrates of Ap-B such as kallidin (14), enkephalins (15,44), and somatostatin (45) might play a central role.…”

HIV‐1 Tat and opiate‐induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP‐1 and alternative chemokines

“…Furthermore, opioids can inhibit the production of RANTES and the migration of microglial cells toward RANTES (Hu et al, 2000;Miyagi et al, 2000). In contrast, opioids have been shown to facilitate chemotaxis in blood mononuclear cells (van Epps and Saland, 1984), as well as leukemia cells (Heagy et al, 1995). Opioid receptors are expressed on cells of the immune system such as the macrophages and T lymphocytes (Chuang et al, 1995;Wick et al, 1996;Sharp, 2003), as well as on microglia and astrocytes Gurwell et al, 2001;Stiene-Martin et al, 2001).…”

Opiate Inhibition of Chemokine‐Induced Chemotaxis

“…For example, the endoge‐nous opioids β‐endorphin and met‐enkephalin are known to be chemotactic for peripheral blood mononuclear cells, 8 as well as for small‐cell lung carcinoma cells, 9 and leukemic cells. 10 More recent provocative data suggest the possibility that opi‐ates might act to inhibit HIV expression in microglial cells. 11 Although apparently conflicting, when taken together these studies do suggest that opiate effects on leukocytes are mediated through specific opiate receptors; indeed recent evidence suggests that morphine may act to inhibit monocyte and neutrophil functions through the physiologically defined μ3 opiate receptor, 12–13 and the expression of δ, κ, and μ subclasses of G protein‐coupled opiate receptors has been detected molecularly in lymphocytes and monocytes.…”