title: Mechanisms for impaired effector function in alveolar macrophages from marijuana and cocaine smokers.
abstract: Lung macrophages provide a first line of host defense against inhaled pathogens and their function is impaired in the lungs of inhaled substance abusers. In order to investigate the mechanism for this impairment, alveolar macrophages (AM) were recovered from nonsmokers (NS), regular tobacco smokers (TS), marijuana smokers (MS), or crack cocaine smokers (CS), and evaluated for their production of nitric oxide (NO) and the role of NO as an antimicrobial effector molecule. AM from NS and TS efficiently killed Staphylococcus aureus and their antibacterial activity correlated closely with the production of nitrite and the expression of mRNA encoding for inducible nitric oxide synthase (iNOS). In contrast, AM collected from MS and CS exhibited limited antimicrobial activity that was not affected by an inhibitor of iNOS, or associated with expression of iNOS. Treatment with either granulocyte/macrophage colony-stimulating factor (GM-CSF) or interferon-gamma restored the ability of these cells to produce NO and to kill bacteria. These findings confirm a significant role for NO as an antibacterial effector molecule used by normal human AM and suggest that this host defense mechanism is suppressed by habitual exposure to inhaled marijuana or crack cocaine in vivo.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roth
authors.forename: Katherine
authors.initials: K
authors.lastname: Whittaker
authors.forename: Ken
authors.initials: K
authors.lastname: Salehi
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Baldwin
mesh_terms: D000328:Adult; D002188:Cannabis / Q000737:chemistry*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008385:Marijuana Smoking / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D013211:Staphylococcus aureus
chemical_list: D009569:Nitric Oxide; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D003042:Cocaine; D019331:NG-Nitroarginine Methyl Ester