Morphine-induced macrophage apoptosis modulates migration of macrophages: use of in vitro model of urinary tract infection.
BACKGROUND
Morphine has been reported to alter immune function. Morphine-induced macrophage apoptosis has been shown to contribute to altered immune status in an opiate milieu. We studied the effect of morphine-induced macrophage apoptosis on the migration of macrophages. Because urinary tract infection (UTI) is one of the commonest infections to evoke an inflammatory response; i.e., migration of neutrophils and monocytes to the site of infection, we used an in vitro model of UTI to test our hypothesis.


METHODS
We carried out both in vivo and in vitro studies. Mice of the FVB/N strain were treated with morphine for short (three doses, 24 hours) and long (11 doses, 96 hours) durations, and their bone marrow cells were isolated. In addition, apoptotic macrophages were prepared by heat treatment. To simulate the in vitro model of UTI, E. coli-activated tubular cell (TC)-conditioned medium containing transforming growth factor-beta (TGF-beta) and macrophage-monocyte chemoattractant protein-1 (MCP-1) was used to test migration of macrophages across a filter in a modified Boyden chamber. In addition, migration of macrophages into the peritoneal cavity was evaluated in both control and morphine-treated states. The effect of morphine on apoptosis as well as migration was studied in murine macrophages and bone marrow cells.


RESULTS
Morphine not only promoted apoptosis of bone marrow cells (20% apoptotic cells) but also inhibited their migration across the filter. Control cells showed minimal apoptosis but displayed greater migration. Similarly, heat-treated (apoptotic) cells showed minimal migration. In peritoneal macrophage studies, morphine treatment retarded migration.


CONCLUSIONS
Morphine inhibits macrophage migration both in vivo and in vitro. This attenuated transmigration of macrophages seems to be secondary to the apoptotic effect of morphine.
Malik
Aftab A
AA
Department of Urology, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
Radhakrishnan
Neetu
N
Reddy
Krishna
K
Smith
Arthur D
AD
Singhal
Pravin C
PC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D004334:Drug Administration Schedule; D004926:Escherichia coli / Q000254:growth & development; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000382:microbiology / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D027383:Papillomaviridae; D010529:Peritoneal Cavity / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014552:Urinary Tract Infections / Q000276:immunology*
D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D009020:Morphine