title: Aluminium lactate treatment of DQ12 quartz inhibits its ability to cause inflammation, chemokine expression, and nuclear factor-kappaB activation.
abstract: In 1997, an IARC Working Group classified quartz (crystalline silica) as a Group 1 lung carcinogen, but only in some industries, i.e., the quartz hazard is a variable entity. The reactivity of the quartz surface may underlie its ability to cause inflammation, and treatments that ameliorate this reactivity will reduce the quartz hazard. In this study we treated quartz (Q) with aluminium lactate (AL), a procedure that is reported to decrease the quartz hazard, and explored the effect this had on the highly reactive quartz surface and on proinflammatory events in rat lungs. Aluminium lactate-treated quartz showed a reduced surface reactivity as measured by electron spin resonance and the hemolysis assay. Eighteen hours after instillation of Q into the rat lung, there was massive inflammation as indicated by the number of neutrophils in the bronchoalveolar lavage (BAL). In addition, Q induced an increase in BAL macrophage inflammatory protein-2 (MIP-2) while ALQ had no significant effect compared to control. Epithelial damage, as indicated by BAL protein and gamma glutamyl transpeptidase, also increased with Q but not with ALQ. Furthermore, Q induced an increase in MIP-2 mRNA by BAL cells while ALQ had no effect compared to controls. There was an increase in nuclear binding of the transcription nuclear factor kappaB (NF-kappaB) in the Q-exposed BAL cells and again no effect on nuclear NF-kappaB binding in BAL cells from ALQ-exposed rats. In conclusion, treatment of the quartz surface with aluminium lactate reduced the reactivity of the particles both in terms of hydroxyl radical generation and in terms of the induction of molecular signaling events leading to inflammation.
authors.affiliation: ELEGI/Colt Laboratories, Department of Respiratory Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Duffin
authors.forename: P S
authors.initials: PS
authors.lastname: Gilmour
authors.forename: R P
authors.initials: RP
authors.lastname: Schins
authors.forename: A
authors.initials: A
authors.lastname: Clouter
authors.forename: K
authors.initials: K
authors.lastname: Guy
authors.forename: D M
authors.initials: DM
authors.lastname: Brown
authors.forename: W
authors.initials: W
authors.lastname: MacNee
authors.forename: P J
authors.initials: PJ
authors.lastname: Borm
authors.forename: K
authors.initials: K
authors.lastname: Donaldson
authors.forename: V
authors.initials: V
authors.lastname: Stone
mesh_terms: D017607:Aluminum Compounds / Q000737:chemistry*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D054426:Chemokine CXCL2; D018925:Chemokines / Q000032:analysis / Q000235:genetics*; D003460:Crystallization; D015870:Gene Expression / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced*; D007773:Lactates / Q000737:chemistry*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects; D008297:Male; D008855:Microscopy, Electron, Scanning; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils; D011791:Quartz / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007773:Lactates; D016328:NF-kappa B; D012333:RNA, Messenger; D011791:Quartz; D017665:Hydroxyl Radical; D005723:gamma-Glutamyltransferase; C104223:aluminum lactate