Opioids suppress chemokine-mediated migration of monkey neutrophils and monocytes - an instant response.
Opioid users having acquired human immunodeficiency syndrome (AIDS) are at a greater risk than non-users of contracting opportunistic infections. Opioid-administered and simian immunodeficiency virus (SIV)-infected rhesus monkeys have been an excellent model for studying AIDS and drug abuse in humans. In this study, chemotaxis of monkey leukocytes was evaluated using the chemokines interleukin-8 (IL-8) and regulated upon activation, normal T cell expressed (RANTES) as the chemoattractants, and the effects of various opioid agonists and antagonists on the efficiency of chemotaxis were examined. Opioids were either incubated with monkey leukocytes or added directly to chemokines, and the number of cells migrating toward IL-8 (for neutrophils) or RANTES (for monocytes) was scored. Inhibition of chemotaxis was seen with both assay conditions, and the inhibition was mediated by opioids binding to mu or kappa receptors. Binding to delta opiod receptors was rarely, if ever, observed. Although opioids themselves may act as weak chemoattractants for monkey leukocytes, addition of opioid agonists to chemokines would reduce the chemoattractant ability of the chemokines. Opioids did not cause the same inhibitory effect on the chemotactic migration of neutrophils when the complement component C5a or the chemotactic peptide N-formyl-MET-LEU-PHE (fMLP) was used as chemoattractant. These studies suggest that the presence of opioids during SIV infection immediately alters chemokine-mediated immune functions.
Miyagi
T
T
Department of Medical Pharmacology and Toxicology, School of Medicine, University of California, Davis, CA 95616, USA.
Chuang
L F
LF
Lam
K M
KM
Kung
H
H
Wang
J M
JM
Osburn
B I
BI
Chuang
R Y
RY
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D018946:Chemokine CCL5 / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology*; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015936:Complement C5a / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016209:Interleukin-8 / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D018946:Chemokine CCL5; D018925:Chemokines; D002630:Chemotactic Factors; D016209:Interleukin-8; D009292:Narcotic Antagonists; D009294:Narcotics; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009020:Morphine; D015936:Complement C5a