Studies on cystic fibrosis using isoelectric focusing. III. Correlation between cystic fibrosis protein and ciliary dyskinesia activity in serum shown by a modified rabbit tracheal bioassay

Abstract

We have developed a modified rabbit tracheal bioassay for use in investigating a possible correlation between cystic fibrosis protein (CFP) and ciliary dyskinesia factor (CDF) in human serum. The bioassay requires high standards of tissue selection, and all epithelial tissue must be free of underlying connective tissue. When serum samples were collected and processed carefully and warmed to 37 degrees before assay, CDF could be reliably detected in 31 of 31 sera from cystic fibrosis (CF) homozygotes or obligate heterozygotes in 35 min or less without prior fractionation or concentration of sera, whereas 13 of 14 normal control sera were nonreactive. CDF-positive serum reacts in three consecutive phases: (1) initial increase in ciliary beat frequency, (2) ciliary dyskinesia, and (3) tissue destruction with extrusion of single ciliated cells, mucus, and debris. Our results confirm the association of CDF with cystic fibrosis. The bioassay is not specific for CF, however, when whole sera are bioassayed, since serum from several patients with bronchial asthma also caused ciliary dyskinesia. However, this finding need not preclude using rabbit tracheal ciliated epithelial tissue as an assay for following the purification of CDF. Isoelectric focusing showed that the presence or absence of CFP corresponded with that of dyskinesia activity in all sera tested except for the active samples from seven asthma patients, which were negative for CFP. The results indicate that CFP and CDF may be identical or closely related markers for the CF gene, and suggest that the activity detected by the rabbit tracheal bioassay in sera from patients with asthma and other diseases probably is caused by a substance different from a CF-specific CDF.