Intranasal exposure to a damp building mould, Stachybotrys chartarum, induces lung inflammation in mice by satratoxin-independent mechanisms.
BACKGROUND
Stachybotrys chartarum is a damp building mould and a potent toxin producer that has been related to serious cases of respiratory health problems. However, the direct link between exposure and health symptoms has not been established.


OBJECTIVE
To examine the mechanism by which exposure to spores of satratoxin producing and non-producing S. chartarum strains induce inflammatory responses in murine lungs.


METHODS
BALB/c mice were intranasally exposed for 3 weeks to spores of a satratoxin-producing and a non-producing S. chartarum strain. Inflammatory cell infiltration was characterized from bronchoalveolar lavage (BAL) fluid. Cytokine and chemokine mRNA expression in lung tissue was measured with real-time PCR. Bronchial responsiveness to methacholine (MCh) was determined by whole-body plethysmography and serum antibody levels by ELISA.


RESULTS
A dose-dependent increase in monocytes, neutrophils and lymphocytes was observed in BAL fluid after intranasal (i.n.) instillation of S. chartarum spores. There was no difference in the BAL between exposure to the satratoxin-producing and the non-producing strains. Infiltration of inflammatory cells was associated with an induction of pro-inflammatory cytokine (IL-1beta, IL-6 and TNF-alpha) and chemokine (CCL3/MIP-1alpha, CCL4/MIP-1beta and CCL2/MCP-1) mRNA levels in the lungs. Interestingly, CXCL5/LIX was the only chemokine that showed significantly higher mRNA levels after exposure to the satratoxin-producing strain compared with the non-producing strain. MCh-induced bronchial responsiveness was not altered significantly after mould instillation. Moreover, no significant increase in total or specific IgE, IgG2a and IgG1 antibody levels were found after S. chartarum exposure.


CONCLUSIONS
These results indicate that lung inflammation induced by i.n. instillations of S. chartarum spores is regulated by the induction of pro-inflammatory cytokines and leucocyte-attracting chemokines. The data also imply that S. chartarum-derived components, other than satratoxins, are mediating the development of this inflammatory response.
Leino
M
M
Finnish Institute of Occupational Health, Helsinki, Finland.
Mäkelä
M
M
Reijula
K
K
Haahtela
T
T
Mussalo-Rauhamaa
H
H
Tuomi
T
T
Hintikka
E-L
EL
Alenius
H
H
D000281:Administration, Intranasal; D000818:Animals; D001985:Bronchial Provocation Tests / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000382:microbiology*; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D009183:Mycotoxins / Q000633:toxicity; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology*; D012333:RNA, Messenger / Q000235:genetics; D013172:Spores, Fungal / Q000472:pathogenicity; D013191:Stachybotrys / Q000472:pathogenicity*
D018925:Chemokines; D016207:Cytokines; D009183:Mycotoxins; D012333:RNA, Messenger; D016210:Methacholine Chloride