title: Acinetobacter baumannii-induced lung cell death: role of inflammation, oxidative stress and cytosolic calcium.
abstract: A growing body of evidence supports the notion that susceptible Acinetobacter baumannii strain ATCC 19606 induces human epithelial cells death. However, most of the cellular and molecular mechanisms associated with this cell death remain unknown, and also the degree of the cytotoxic effects of a clinical panresistant strain compared with a susceptible strain has never been studied. Due to the role of proinflammatory cytokine release, oxidative stress and cytosolic calcium increase in the cell death-induced by other Gram-negative bacteria, we investigated whether these intracellular targets were involved in the cell death induced by clinical panresistant 113-16 and susceptible ATCC 19606 strains. Data presented here show that 113-16 and ATCC 19606 induce time-dependent cell death of lung epithelial cells involving a perturbation of cytosolic calcium homeostasis with subsequent calpain and caspase-3 activation. Prevention of this cell death by TNF-α and interleukin-6 blockers and antioxidant highlights the involvement of proinflammatory cytokines and oxidative stress in this phenomenon. These results demonstrate the involvement of calpain calcium-dependent in cell death induced by A. baumannii and the impact of proinflammatory cytokines and oxidative stress in this cell death; it is noteworthy to stress that some mechanisms are less induced by the panresistant strain.
authors.affiliation: Service of Infectious Diseases, Institute of Biomedicine of Sevilla, University Hospital Virgen del Rocío/CSIC/University of Sevilla, Av. Manuel Siurot s/n, 41013 Sevilla, Spain. younes.smani.exts@juntadeandalucia.es
authors.forename: Younes
authors.initials: Y
authors.lastname: Smani
authors.forename: Fernando
authors.initials: F
authors.lastname: Docobo-Pérez
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McConnell
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Pachón
mesh_terms: D040981:Acinetobacter baumannii / Q000472:pathogenicity*; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D018384:Oxidative Stress; D013997:Time Factors
chemical_list: D002154:Calpain; D053148:Caspase 3; D002118:Calcium