title: Pulmonary responses to Stachybotrys chartarum and its toxins: mouse strain affects clearance and macrophage cytotoxicity.
abstract: We investigated differences in the pulmonary and systemic clearance of Stachybotrys chartarum spores in two strains of mice, BALB/c and C57BL/6J. To evaluate clearance, mice were intratracheally instilled with a suspension of radiolabeled S. chartarum spores or with unlabeled spores. The lungs of C57BL/6J mice showed more rapid spore clearance than the lungs of BALB/c mice, which correlated with increased levels of spore-associated radioactivity in the GI tracts of C57BL/6J as compared with BALB/c mice. To identify mechanisms responsible for mouse strain differences in spore clearance and previously described lung inflammatory responses, we exposed alveolar macrophages (AMs) lavaged from BALB/c and C57BL/6J mice to S. chartarum spores, S. chartarum spore toxin (SST), and satratoxin G (SG) in vitro. The S. chartarum spores were found to be highly toxic with most cells from either mouse strain being killed within 24 h when exposed to a spore:cell ratio of 1:75. The spores were more lethal to AMs from C57BL/6J than those from BALB/c mice. In mice, the SST elicited many of the same inflammatory responses as the spores in vivo, including AM recruitment, pulmonary hemorrhage, and cytokine production. Our data suggest that differences in pulmonary spore clearance may contribute to the differences in pulmonary responses to S. chartarum between BALB/c and C57BL/6J mice. Enhanced AM survival and subsequent macrophage-mediated inflammation may also contribute to the higher susceptibility of BALB/c mice to S. chartarum pulmonary effects. Analogous genetic differences among humans may contribute to reported variable sensitivity to S. chartarum.
authors.affiliation: Department of Environmental Health, Program in Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, Massachusetts 02115, USA. jrosenbl@hsph.harvard.edu
authors.forename: Jamie H Rosenblum
authors.initials: JH
authors.lastname: Lichtenstein
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Molina
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Donaghey
authors.forename: Chidozie J
authors.initials: CJ
authors.lastname: Amuzie
authors.forename: James J
authors.initials: JJ
authors.lastname: Pestka
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Brain
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009183:Mycotoxins / Q000633:toxicity*; D013045:Species Specificity; D013172:Spores, Fungal / Q000502:physiology; D013191:Stachybotrys / Q000502:physiology*
chemical_list: D009183:Mycotoxins
references.citation: Toxicol Sci. 2005 Mar;84(1):186-94
references.pmid: 15574675
references.citation: Mycopathologia. 2003;156(2):119-31
references.pmid: 12733633
references.citation: J Immunol. 2003 Nov 15;171(10):5380-8
references.pmid: 14607941
references.citation: Clin Diagn Lab Immunol. 2003 Mar;10(2):259-66
references.pmid: 12626452
references.citation: J Toxicol Environ Health A. 2005 Aug 13;68(15):1321-35
references.pmid: 16020192
references.citation: Mycopathologia. 2008 Feb;165(2):73-80
references.pmid: 18046622
references.citation: Int J Exp Pathol. 1996 Oct;77(5):213-8
references.pmid: 8977373
references.citation: Toxicol Mech Methods. 2003;13(4):247-52
references.pmid: 20021149
references.citation: Science. 1998 Dec 11;282(5396):2085-8
references.pmid: 9851930
references.citation: J Toxicol Environ Health. 1993 Feb;38(2):183-98
references.pmid: 8433402
references.citation: Arch Pediatr Adolesc Med. 1998 Aug;152(8):757-62
references.pmid: 9701134
references.citation: Fundam Appl Toxicol. 1997 Feb;35(2):182-8
references.pmid: 9038239
references.citation: J Toxicol Environ Health A. 2009;72(20):1242-51
references.pmid: 20077192
references.citation: Infect Immun. 1988 Jan;56(1):13-7
references.pmid: 3335400
references.citation: Adv Appl Microbiol. 2004;55:241-73
references.pmid: 15350797
references.citation: Toxicology. 2007 Jun 3;235(1-2):92-102
references.pmid: 17420079
references.citation: Int J Biochem Cell Biol. 2006;38(11):1848-54
references.pmid: 16844403
references.citation: Mycologia. 2003 Nov-Dec;95(6):1227-38
references.pmid: 21149024
references.citation: Toxicol Appl Pharmacol. 2006 Aug 1;214(3):297-308
references.pmid: 16476459
references.citation: J Immunol. 2001 Nov 1;167(9):5084-91
references.pmid: 11673518
references.citation: J Immunol. 2006 Nov 1;177(9):6480-8
references.pmid: 17056580
references.citation: Toxicol Appl Pharmacol. 2009 Jun 1;237(2):137-45
references.pmid: 19306889
references.citation: Toxicol Sci. 2008 Jul;104(1):4-26
references.pmid: 18007011
references.citation: Mycopathologia. 2007 Oct;164(4):171-81
references.pmid: 17610048
references.citation: Inflamm Res. 1996 Mar;45 Suppl 1:S23-4
references.pmid: 8696913
references.citation: Occup Environ Med. 1998 Sep;55(9):579-84
references.pmid: 9861178
references.citation: Infect Immun. 1989 Dec;57(12):3788-92
references.pmid: 2509369
references.citation: Toxicology. 2003 Apr 15;186(1-2):51-65
references.pmid: 12604170
references.citation: Am J Respir Cell Mol Biol. 1995 Oct;13(4):487-95
references.pmid: 7546779
references.citation: Infect Immun. 2007 Oct;75(10):4792-8
references.pmid: 17664261
references.citation: Mycopathologia. 2000 Jan;149(1):27-34
references.pmid: 11227851
references.citation: Infect Immun. 2002 Apr;70(4):2065-9
references.pmid: 11895972
references.citation: Apoptosis. 2007 Mar;12(3):535-48
references.pmid: 17186382
references.citation: Toxicol Sci. 2009 Jun;109(2):247-55
references.pmid: 19336499
references.citation: Infect Immun. 2005 Jan;73(1):114-25
references.pmid: 15618146
references.citation: Am J Respir Cell Mol Biol. 2006 Oct;35(4):415-23
references.pmid: 16690987
references.citation: Environ Health Perspect. 2006 Jul;114(7):1099-107
references.pmid: 16835065
references.citation: Toxicol Sci. 2002 Feb;65(2):239-45
references.pmid: 11812928
references.citation: Appl Environ Microbiol. 2003 Jul;69(7):3751-7
references.pmid: 12839740
references.citation: Mycologia. 2002 May-Jun;94(3):392-403
references.pmid: 21156510
references.citation: Toxicol Sci. 2002 Nov;70(1):98-109
references.pmid: 12388839
references.citation: Electron J Stat. 2009 Jan 1;3:1193-1256
references.pmid: 20305800
references.citation: Pediatr Pulmonol. 2007 Jul;42(7):592-9
references.pmid: 17534970
references.citation: Toxicol Sci. 2008 Sep;105(1):142-52
references.pmid: 18535002
references.citation: Infect Immun. 2004 Aug;72(8):4801-9
references.pmid: 15271942
references.citation: Science. 1979 May 4;204(4392):514-7
references.pmid: 432655
references.citation: Infect Immun. 1998 Oct;66(10):4994-5000
references.pmid: 9746609
references.citation: Pediatrics. 2002 Sep;110(3):627-37
references.pmid: 12205270
references.citation: Infect Immun. 2007 Jun;75(6):2729-39
references.pmid: 17371865
references.citation: J Toxicol Environ Health A. 2006 Jul;69(13):1239-51
references.pmid: 16754538
references.citation: J Immunol. 2009 May 15;182(10):6418-25
references.pmid: 19414795
references.citation: Infect Immun. 2008 Sep;76(9):4241-50
references.pmid: 18625738
references.citation: BMC Immunol. 2003 Jun 26;4:5
references.pmid: 12826024
references.citation: Environ Health Perspect. 1999 Jun;107 Suppl 3:495-9
references.pmid: 10346998