title: Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria.
abstract: Electronic (e)-cigarette use is rapidly rising, with 20 % of Americans ages 25-44 now using these drug delivery devices. E-cigarette users expose their airways, cells of host defense, and colonizing bacteria to e-cigarette vapor (EV). Here, we report that exposure of human epithelial cells at the air-liquid interface to fresh EV (vaped from an e-cigarette device) resulted in dose-dependent cell death. After exposure to EV, cells of host defense-epithelial cells, alveolar macrophages, and neutrophils-had reduced antimicrobial activity against Staphylococcus aureus (SA). Mouse inhalation of EV for 1 h daily for 4 weeks led to alterations in inflammatory markers within the airways and elevation of an acute phase reactant in serum. Upon exposure to e-cigarette vapor extract (EVE), airway colonizer SA had increased biofilm formation, adherence and invasion of epithelial cells, resistance to human antimicrobial peptide LL-37, and up-regulation of virulence genes. EVE-exposed SA were more virulent in a mouse model of pneumonia. These data suggest that e-cigarettes may be toxic to airway cells, suppress host defenses, and promote inflammation over time, while also promoting virulence of colonizing bacteria.
  
  
  
  Acute exposure to e-cigarette vapor (EV) is cytotoxic to airway cells in vitro. Acute exposure to EV decreases macrophage and neutrophil antimicrobial function. Inhalation of EV alters immunomodulating cytokines in the airways of mice. Inhalation of EV leads to increased markers of inflammation in BAL and serum. Staphylococcus aureus become more virulent when exposed to EV.
authors.affiliation: Pulmonary and Critical Care Section, VA San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111J, San Diego, CA, 92161, USA.|Department of Medicine, Division of Pulmonary and Critical Care, University of California at San Diego (UCSD), La Jolla, CA, 92093, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Pulmonary and Critical Care Section, VA San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111J, San Diego, CA, 92161, USA.|Duke University School of Medicine, Durham, NC, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lyes
authors.affiliation: Pulmonary and Critical Care Section, VA San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111J, San Diego, CA, 92161, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Sladewski
authors.affiliation: Pulmonary and Critical Care Section, VA San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111J, San Diego, CA, 92161, USA.|Microbiology and Immunology Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
authors.forename: Shymaa
authors.initials: S
authors.lastname: Enany
authors.affiliation: Pulmonary and Critical Care Section, VA San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111J, San Diego, CA, 92161, USA.|Weill Cornell Medical College, New York, NY, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: McEachern
authors.affiliation: Pulmonary and Critical Care Section, VA San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111J, San Diego, CA, 92161, USA.
authors.forename: Denzil P
authors.initials: DP
authors.lastname: Mathew
authors.affiliation: Departments of Pathology and Medicine, UCSD, La Jolla, CA, 92093, USA.
authors.forename: Soumita
authors.initials: S
authors.lastname: Das
authors.affiliation: Pulmonary and Critical Care Section, VA San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111J, San Diego, CA, 92161, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Moshensky
authors.affiliation: Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
authors.forename: Sagar
authors.initials: S
authors.lastname: Bapat
authors.affiliation: Departments of Pathology and Medicine, UCSD, La Jolla, CA, 92093, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Pride
authors.affiliation: Division of Head and Neck Surgery, Department of Surgery, UCSD, La Jolla, CA, 92093, USA.
authors.forename: Weg M
authors.initials: WM
authors.lastname: Ongkeko
authors.affiliation: Pulmonary and Critical Care Section, VA San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111J, San Diego, CA, 92161, USA. lcrotty@ucsd.edu.|Department of Medicine, Division of Pulmonary and Critical Care, University of California at San Diego (UCSD), La Jolla, CA, 92093, USA. lcrotty@ucsd.edu.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Crotty Alexander
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D016923:Cell Death / Q000187:drug effects; D045424:Complex Mixtures / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D066300:Electronic Nicotine Delivery Systems; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D045424:Complex Mixtures; D016207:Cytokines; D012906:Smoke; D054804:Cathelicidins
keywords: Antimicrobial peptide LL-37; Cytotoxicity; E-cigarette vapor; Inflammatory lung disease; MRSA pneumonia; Staphylococcal virulence