Mouse strain affects Stachybotrys chartarum induced alveolar macrophage cytotoxicity (51.9)

• Published in: The Journal of immunology (1950) 2007-04, Vol.178 (1_Supplement), p.S98-S98
• Main Authors: Lichtenstein, Jamie H Rosenblum, Donaghey, Thomas C, Molina, Ramon M, Brain, Joseph D.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.178.Supp.51.9

The fungus Stachybotrys chartarum (S. chartarum) releases mycotoxins that can cause lung injury, inflammation, hemorrhage and cytotoxicity. We have shown that when BALB/c mice receive instilled spores, they have greater lung inflammation, hemorrhage, and cytokine production and less efficient spore clearance than C57BL/6J mice. To investigate these mouse strain differences, we exposed alveolar macrophages (AMs) lavaged from these two strains of mice to spores in vitro. Then the cells were stained with calcein AM (live) and EthD1 (dead), and images were collected on a BD Pathway Bioimager. Both strains exhibited increasing AM death as doses increased from 200 to 5000 spores per 75,000 AMs (p=0.0001) with more C57BL/6J than BALB/c AMs dying (slopes significantly different at p=0.007). After one day, 84 ± 4% of C57BL/6J AMs versus 66 ± 5% of BALB/c AMs died at the 1000:75,000 spores:AMs dose. The spores killed C57BL/6J AMs sooner (p=0.04) than BALB/c AMs. Many of the dead AMs from both strains appear morphologically apoptotic. In vivo, AM death may diminish cytokine levels and inflammation in C57BL/6J mice because dead cells do not synthesize cytokines. This increased cytotoxicity coupled with improved spore clearance, causing a lower effective spore dose, may reduce inflammation in C57BL/6J mice. Analogous differences may contribute to the range of sensitivity to S. chartarum seen among humans.