Effects of Stachybotrys chartarum on surfactant convertase activity in juvenile mice

We have shown recently that alveolar type II cells are sensitive to exposur e to Stachybotrys chartarum spores, both in vitro and in an in vivo juvenil e mouse model. In mice, this sensitivity is manifest in part as a significa nt increase in the newly secreted, biologically active, heavy aggregate for m of alveolar surfactant (H) and the accumulation of the lighter, "metaboli cally used", biologically inactive alveolar surfactant forms (L-vivo) in th e interalveolar space. Conversion of the heavy, surface-active alveolar sur factant to the light metabolically used, nonsurface active forms is believe d to involve the activity of an enzyme, namely convertase, which is thought to be derived from lamellar bodies (LB) in alveolar type II cells. The pur pose of this study was to evaluate the effects of S. chartarum spores on mo use H and LE convertase activity by measuring their rates of conversion to L-vivo using the in vitro surface area cycling technique. It was determined whether there were concurrent changes in the protein and phospholipid conc entrations of the raw bronchoalveolar lavage fluid (RL) and LB fractions th at could be correlated with changes in convertase activity. Conversions of H to L,,, in untreated control mice and saline-, isosatratoxin F-, and Clad osporium cladosporioides-exposed mice were not significantly different (p > 0.05). However, conversion from H to L,,, in the mice exposed to S. charta rum spores was significantly higher than all other treatment groups (p < 0. 001). LB to L-vivo conversions in untreated and saline-exposed mice were no t significantly different, although they were significantly higher than the H to L-vivo conversions in these two animal treatment groups (p < 0.005), which supports the position that LB is a source of convertase activity in a nimals. LB to L-vivo conversion from C. cladosporioides-, isosatrotoxin F-, and S. chartarum-exposed mice were all significantly depressed (p < 0.003) compared to the LB to L-vivo conversion values obtained from untreated and saline-exposed mice. Protein concentrations in RL, H, L-vivo and LB from m ice exposed to S. chartarum spores were significantly elevated compared to those from the other treatment groups (p < 0.001). Protein concentration in H isolated from C. cladosporioides-exposed mice was also significantly ele vated above untreated and saline control animal levels. Phospholipid concen trations in H isolated from S. chartarum-exposed mice were significantly el evated compared to those from other treatment groups, while LB phospholipid concentrations were significantly increased compared to saline and untreat ed control animal groups. These results show that S. chartarum spores signi ficantly alter convertase activity in both the H and LB surfactant fraction s in juvenile mice and that these changes can be related to changes in prot ein and phospholipid concentrations in alveolar lavage fractions. As surfac tant promotes lung stability by reducing the surface tension of the air-alv eolar interface, these results further support our position that inhalation exposure to S. chartarum spores in exposed individuals may lead to altered surfactant metabolism, and possibly to lung dysfunction through diminished alveolar surfactant surface tension attributes, and lung stability. (C) 20 01 Academic Press.