Title: Mouse strain differences influence pulmonary responses to Stachybotrys chartarum
Description: When the fungus Stachybotrys chartarum is inhaled, its mycotoxins may cause lung injury and inflammation. The severity of mammalian responses attributed to S. chartarum varies widely. To explore these differences, we intratracheally instilled C3H/HeJ, BALB/c, and C57BL/6J mice, with S. chartarum spores suspended in saline. One day later, biochemical and cellular indicators of lung injury and inflammation were measured. BALB/c mice showed the highest myeloperoxidase activity, albumin and hemoglobin levels, and neutrophil numbers in their BAL among the three strains. BALB/c was the only strain to show significant increases in KC, MCP-1, MCP-3, MIP-1[alpha], MIP-1[beta], MIP-1[gamma], MIP-2, RANTES, IL-1[alpha], IL-1[beta], IL-3, IL-6, IL-18, LIF, M-CSF, and TNF[alpha]. We also assessed whether underlying pulmonary allergic inflammation might alter susceptibility to S. chartarum induced pulmonary inflammation and injury. Surprisingly, in BALB/c mice, ovalbumin-induced airway inflammation partially mitigated some of these mold-induced pulmonary responses.

We also investigated strain-related differences in the clearance of S. chartarum . BALB/c and C57BL/6J mice were intratracheally instilled with 14 C glucose and 3 H thymidine labeled S. chartarum spores suspended in saline. These two strains were also instilled with unlabeled spores, to evaluate the persistence of whole spores morphologically. C57BL/6J mice showed more rapid pulmonary spore clearance than did BALB/c mice by both procedures. Moreover, more spore-related radioactivity appeared in the GI-track of C57BL/6J than BALB/c mice. Next, we exposed cultured murine alveolar macrophages (AMs) from these two strains to spores in vitro. The spores were highly toxic. A ratio of one spore to seventy-five cells dramatically reduced cell survival in both strains of mice after 24 hours. The spores proved more lethal to AMs from C57BL/6J than BALB/c mice. Our data suggest that pulmonary spore clearance is a critical determinant of pulmonary responses to S. chartarum . BALB/c and C57BL/6J differ in regard to in vivo inflammatory responses as well as AM survival. Analogous underlying genetic differences may contribute to the wide range of susceptibility to Stachybotrys hypothesized among humans.