title: Effects of benzalkonium chloride on THP-1 differentiated macrophages in vitro.
abstract: OBJECTIVE
  To characterize the effects of benzalkonium chloride (BAK) in THP-1 differentiated cells in vitro.
  
  
  METHODS
  Macrophages were obtained after differentiation of THP-1 cells, a human monocytic leukemia cell line. Macrophages were exposed for 24 h to 33 nM (10(-5)%) benzalkonium chloride (BAK), 10 nM dinitrochlorobenzene (DNCB), 100 ng/mL lipopolysaccharide (LPS), 5 ng/mL tumor necrosis factor alpha (TNF-α) or phosphate buffered saline (PBS) as controls. The expression of CD11b, CD11c, CD33 and CD54 was evaluated using immunohistochemistry and flow cytometry (FCM). Phagocytosis function was analyzed using carboxylate-modified fluorescent microspheres and quantified by FCM. Migration was evaluated in cocultures with conjunctival epithelial cells. Cytokine production was detected and quantified in culture supernatants using a human cytokine array.
  
  
  RESULTS
  Stimulation of THP-1-derived macrophages with a low concentration of BAK increased CD11b and CD11c expression and decreased CD33. Macrophages exposed to BAK, LPS and TNF-α had increased phagocytosis. In contrast to LPS, BAK and TNF-α increased macrophage migration. Cytokines in supernatants of macrophages exposed to BAK revealed an increased release of CCL1, CCL4/MIP-1β, TNF-α, soluble CD54/ICAM-1 and IL-1β.
  
  
  CONCLUSIONS
  In vitro, BAK has a direct stimulating effect on macrophages, increasing phagocytosis, cytokine release, migration and expression of CD11b and CD11c. Long-term exposure to low concentrations of BAK should be considered as a stimulating factor responsible for inflammation through macrophage activation.
authors.affiliation: INSERM, U968, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Michée
authors.forename: Françoise
authors.initials: F
authors.lastname: Brignole-Baudouin
authors.forename: Luisa
authors.initials: L
authors.lastname: Riancho
authors.forename: William
authors.initials: W
authors.lastname: Rostene
authors.forename: Christophe
authors.initials: C
authors.lastname: Baudouin
authors.forename: Antoine
authors.initials: A
authors.lastname: Labbé
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008856:Microscopy, Fluorescence; D010587:Phagocytosis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D001548:Benzalkonium Compounds; D013755:Tetradecanoylphorbol Acetate