title: In vivo morphine treatment synergistically increases LPS-induced caspase activity in immune organs.
abstract: Caspases are a family of proteins important for the elimination of infected cells through the induction of apoptosis as well as the initiation of inflammatory cytokines including IL-1β and IL-18. Morphine exposure to animals and/or cells has been associated with the induction of apoptosis. The most common practices of apoptosis detection have involved removing tissues from animal or humans and the analysis of apoptosis on cells or tissues. These methods can potentially induce spontaneous apoptosis that is unrelated to the actual treatment. The objective of this study was to develop an in vivo detection method for assessing caspase activity induced both by morphine directly and by morphine combined with lipopolysaccharide (LPS)-immune activation. Mice were administered saline, morphine, LPS, or a combination of morphine and LPS. Prior to sacrifice, mice were injected with a polycaspase-specific apoptosis detection probe to detect internal caspase activity in vivo. Results revealed that morphine alone did not directly induce caspase activity. However, morphine significantly enhanced the LPS-induced caspase activity in spleen, thymus, and bone marrow-derived immune cells. The use of a poly-caspase detection probe methodology to label caspase activity in vivo provides a powerful quantitative tool for the in vivo analysis of caspase activity.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA. olin0012@umn.edu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Olin
authors.forename: Sabita
authors.initials: S
authors.lastname: Roy
authors.forename: Thomas
authors.initials: T
authors.lastname: Molitor
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D002469:Cell Separation; D004357:Drug Synergism; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D007150:Immunohistochemistry / Q000379:methods*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008221:Lymphoid Tissue / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D009020:Morphine; D020169:Caspases
references.citation: Anesth Analg. 1999 Nov;89(5):1209-15
references.pmid: 10553836
references.citation: J Neuroimmunol. 2004 Jan;146(1-2):13-21
references.pmid: 14698842
references.citation: Exp Cell Res. 2000 Aug 25;259(1):308-13
references.pmid: 10942603
references.citation: Cytometry. 2001 May 1;44(1):73-82
references.pmid: 11309811
references.citation: J Neurosci. 2002 Sep 1;22(17):7650-61
references.pmid: 12196588
references.citation: FEBS Lett. 1999 Jun 25;453(3):356-60
references.pmid: 10405175
references.citation: Mol Pathol. 1998 Aug;51(4):204-8
references.pmid: 9893746
references.citation: J Infect Dis. 2003 Jan 1;187(1):47-54
references.pmid: 12508145
references.citation: Am J Physiol Renal Physiol. 2003 Nov;285(5):F861-9
references.pmid: 12812915
references.citation: J Neuroimmunol. 1999 Mar 1;95(1-2):107-14
references.pmid: 10229120
references.citation: Neuropharmacology. 2002 May;42(6):829-36
references.pmid: 12015209
references.citation: J Histochem Cytochem. 1996 Dec;44(12):1363-72
references.pmid: 8985128
references.citation: Life Sci. 1998;63(24):2167-74
references.pmid: 9851308
references.citation: Biotechniques. 2003 Nov;35(5):1080-5
references.pmid: 14628683
references.citation: J Leukoc Biol. 2001 Oct;70(4):527-36
references.pmid: 11590188
references.citation: Exp Cell Res. 2000 Jun 15;257(2):290-7
references.pmid: 10837143
references.citation: FEBS Lett. 1997 Jul 7;411(1):77-82
references.pmid: 9247146
references.citation: J Neurochem. 2001 Apr;77(1):182-9
references.pmid: 11279274
references.citation: J Neuroimmunol. 2004 Apr;149(1-2):90-100
references.pmid: 15020069
references.citation: Br J Pharmacol. 2001 Nov;134(6):1263-70
references.pmid: 11704646
references.citation: J Neurosci Res. 2006 May 15;83(7):1352-61
references.pmid: 16496378
references.citation: Life Sci. 2006 Aug 1;79(10):972-80
references.pmid: 16750225
references.citation: Am J Physiol Cell Physiol. 2001 Nov;281(5):C1596-603
references.pmid: 11600423
references.citation: Food Chem Toxicol. 2007 Mar;45(3):486-93
references.pmid: 17092622
references.citation: Nature. 1999 Jan 21;397(6716):218
references.pmid: 9930695
references.citation: Hepatology. 2002 Jan;35(1):40-8
references.pmid: 11786958
references.citation: Int J Immunopharmacol. 1999 Mar;21(3):185-93
references.pmid: 10348368
references.citation: J Clin Anesth. 1996 Mar;8(2):144-50
references.pmid: 8695098
references.citation: J Pathol. 2003 Feb;199(2):221-8
references.pmid: 12533835
references.citation: J Immunol. 1998 Feb 15;160(4):1886-93
references.pmid: 9469450
references.citation: Lancet. 1999 May 15;353(9165):1695-700
references.pmid: 10335806
references.citation: Brain Behav Immun. 2000 Sep;14(3):170-84
references.pmid: 10970678