Mucus-stimulating activity in the sera of patients with cystic fibrosis: demonstration and preliminary fractionation.

The ciliated, mucus-secreting urn cell complex (UCC) is found swimming in the coelomic cavity of the marine invertebrate Sipunculus nudus. This cell complex, which can be maintained in suspension cultures, responds to various stimuli by hypersecreting mucus in the form of a cohesive mucus "tail." This tail can be measured and expressed as a multiple of "urn cell diameters." Using this bioassay, heated sera from 35 patients with cystic fibrosis (CF), 29 patients who were obligate heterozygotes for the CF gene, and 42 controls with a variety of diseases were tested. Control sera yielded a mean (+/- S.D.) mucus tail length of 2.5 (+/-2.3); CF sera yielded a mean mucus tail length of 7.5 (+/- 2.9), (P < 0.0005), and obligate heterozygote sera yielded a mucus tail length of 6.2 (+/- 2.1), (P < 0.0005). These responses were reproducible with different UCC suspensions from the same Sipunculus, as well as from different Sipunculi. In addition, sera from 3 CF patients and 3 controls were chromatographed on protein A-Sepharose. The bound IgG fraction was then washed with 8 M urea and subsequently eluted with 1 M acetic acid. Pooled dialyzed, lyophilized fractions were assayed as coded samples in the UCC assay. Mucus-stimulating activity as measured by mucus tail length per mg protein was greatest in the fractions eluted with 8 M urea. The 8 M urea fractions from 3 CF sera were 2.8 to 5.5 times as active as fractions from 3 control sera. The UCC assay can quantitatively measure mucus-stimulating activity in CF serum. This activity appears to be associated with a serum fraction which can be dissociated from IgG.