Strain Differences Influence Murine Pulmonary Responses toStachybotrys chartarum

Abstract

When the fungus Stachybotrys chartarum is inhaled, its mycotoxins may cause lung injury and inflammation. The severity of human responses to S. chartarum in both occupational and home settings 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, the mice were humanely killed, bronchoalveolar lavage (BAL) was performed, and 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 keratinocyte-derived cytokine (KC), monocyte chemotactic protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-1gamma, MIP-2, RANTES, IL-1alpha, IL-1beta, IL-3, IL-6, IL-18, leukemia inhibitory factor, macrophage colony-stimulating factor, and TNF-alpha. A model of allergen-induced airway inflammation was examined to assess whether underlying allergic inflammation might contribute to increased susceptibility to S. chartarum-induced pulmonary inflammation and injury. Surprisingly, in BALB/c mice, ovalbumin-induced airway inflammation produced a protective effect against some S. chartarum-induced pulmonary responses. This is the first report of mammalian strain differences affecting responses to S. chartarum. These responses differ from those reported for LPS and other fungi. Analogous underlying genetic differences may contribute to the wide range of sensitivity to Stachybotrys among humans.

Repeated Mouse Lung Exposures toStachybotrys chartarumShift Immune Response from Type 1 to Type 2

“…For some biomarkers, single-dosed mice were not significantly different from saline controls. The dose we used was 10-to 100-fold lower than those of our previous studies that used a single instillation (13). Even when combined, the cumulative spore dose for the multipledosed group was still lower than the single dose of prior studies.…”

“…involved only a single acute exposure (10)(11)(12)(13)(14)(15). Few studies include multiple exposures to intact S. chartarum; we found four (16)(17)(18)(19).…”

Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung

“…The noted values represent assessments in a minimum of four infants at each time point. **P < 0.01; # P , 0.02; ## P < 0.05. other model systems (40)(41)(42)(43), as well as the timing. Importantly, our studies also demonstrate that the effects on surfactant were not mediated by NO, as they were not altered by the NOSbased intervention that was employed.…”

Linking lung function and inflammatory responses in ventilator-induced lung injury

“…2) between the three strains. IL-6 levels were significantly higher in BALB/c [79 (22) (20) pg/ml], however, there was no difference between these two strains (P ϭ 0.79; Fig. 2).…”

“…In BALB/c mice, there was a decrease in TNF-␣ levels in the BAL for both ventilation strategies [LVP, 100 (20) pg/ml, P ϭ 0.01; HVZP, 50 (40) pg/ml, P ϭ 0.04]. In contrast, mechanical ventilation was not associated with changes in TNF-␣ levels in 129/Sv mice (P ϭ 0.38), whereas in C57BL/ 6 mice, TNF-␣ levels were significantly lower in LVP-ventilated mice [P Ͻ 0.001; 90 (50) pg/ml] but not in HVZPventilated mice [P ϭ 0.68; 160 (20) pg/ml] compared with naïve controls (Fig.…”