The effects of normal and cystic fibrosis blood serum on mucus secretion and epithelial ultrastructure in rabbit trachea

The effects of cystic fibrosis serum and normal serum on fresh tracheal rings was examined using scanning and transmission electron microscopy. No damage was observed when epithelium was exposed for 60 minutes to normal serum but when epithelium was exposed to cystic fibrosis serum, well-defined cytotoxic changes occured.

As observed by scanning electron microscopy, mucus production was stimulated by homozygote serum after only 3 minutes exposure. With increased length of exposure, eptihelial crevices filled with mucus, creating a net-like structure. Further mucus secretion and accumulation produced thick strands on the cell surface that eventually fused. By 60 minutes exposure, the epithelial surface was covered with a thick mucus net and many areas showed a high columnar cell loss with some exposure of the basement membrane. Differences between effects of sera from heterozygotes and the homozygotes were not in degree of damage, but in the length of exposure required to produce given effects.

Ultrastructural alterations visible with transmission electron microscopy were also observed. The homozygote and the heterozygote sera produced the same changes during the earlier exposures, but they were more numerous with utilization of sera from homozygotes. During the later exposures, the homozygote sera produced much more extensive cell loss and mucus accumulations than did the heterozygote sera. Major changes included a variety of ciliary alterations, extreme dilation of the granular endoplasmic reticulum, mucus iv

consistency alterations, swollen and contorted mitochondria, and cell loss from the basement membrane.

These changes are discussed in terms of their relationship with the membrane permeability and the possibilities of their use as a screening mechanism for cystic fibrosis heterozygote detection in the population.