Specificity of an Isolated Salivary Factor Material to Cystic Fibrosis

Impero, J E; Harrison, Gunyon M.; Nelson, Thomas E.

doi:10.1203/00006450-198106000-00012

Cited by 4 publications

(1 citation statement)

References 12 publications

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“…In the difficult search for a molecular component which might be the CF causative agent, perhaps the most consistent finding has been that serum from CF patients contains a factor which may be responsible for the etiology of the disease (Gabridge et al, 1979;Nagy et al, 1979;Kurlandsky et al, 1980;Impero et al, 1981;McNeely et al, 1982;Carson and Bowman, 1982; Mc-Pherson et al, 1983). Such factors have been isolated by 0 1984 ALAN R. LISS, INC several groups on the basis of their ability to inhibit ciliary activity in tracheal explants or oyster gills (Conover and Conod, 1978;McNeely et al, 1982; Carson and Bowman, 1982), and have proved to be low molecular weight (5-10 kdaltons), cationic glycoproteins reportedly associated with IgG (Danes, 1973;Blitzer and Shapira, 1982).…”

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Effects of cystic fibrosis serum on calcium influx and secretion using isolated tracheal epithelial cells

Wooten

Rudick

et al. 1984

Journal Cellular Physiology

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Hamster trachea epithelial (HTE) cells were shown to respond to 20% cystic fibrosis serum (CFS) by secreting twice as much protein as in the presence of 20% normal human serum (NHS). Serum from obligate heterozygotes (HHS) produced an intermediate effect. A peak of Ca2+ entry into the HTE cells occurred about 30 min after exposure to 20% CFS, followed by a slow decline to basal levels. In contrast, 20% NHS did not cause an influx of Ca2+ and HHS produced an influx to about half that of CFS. Increasing concentrations (5-30%) of pooled NHS had no effect on HTE cell Ca2+ uptake or secretion, but pooled CFS and HHS caused progressive increases in Ca2+ influx and protein secretion from 10 to 25% sera. The CFS-induced Ca2+ influx and secretion were about twice those of HHS throughout the range of serum concentrations tested, suggesting the presence of a modulatory influence in HHS. When EGTA was used to chelate extracellular Ca2+ in the presence of CFS, Ca2+ influx was prevented and there was no stimulation of secretion. Ionophore A23187 allowed Ca2+ entry into HTE cells in the presence or absence of serum and a heightened level of secretory activity followed. The time course of Ca2+ influx under the influence of CFS was shown to correspond to the efflux of Na+ from the cells. Also verapamil, a Ca2+ channel blocking agent, inhibited CFS-induced Ca2+ influx by 50% at 10(-5)M and prevented secretion. Thus, it appears that CFS, but not NHS, contains an agent which stimulates Ca2+ uptake into HTE cells by means of a Ca2+ channel and/or Na+-Ca2+ exchange mechanism, and that increased intracellular Ca2+ levels then trigger secretion. The intermediate HTE cell response to HHS suggests that half of the CFS stimulatory agent is present as would be expected in a gene dose effect, lending support for a genetic basis for CF.

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Effects of cystic fibrosis serum on calcium influx and secretion using isolated tracheal epithelial cells

Wooten

Rudick

et al. 1984

Journal Cellular Physiology

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The effects of proteins secreted by fibroblasts from patients with cystic fibrosis on hamster tracheal explants

Wooten

Rudick

et al. 1985

In Vitro Cell Dev Biol

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Hamster tracheal explants have been used to assay for mucosecretory activity in media taken from cultures of fibroblasts isolated from patients with cystic fibrosis (CF). Cystic fibrosis and normal sera were first used to establish optimal conditions for mucus release in the hamster tracheal ring assay. Unless protein levels were maintained at 5% serum concentration or greater there was loss of cilia, nonspecific mucus accumulation, and extensive epithelial damage to the luminal surface. Likewise, it was shown that exposure of the explants to unconcentrated conditioned media from CF (GM 770, 768, 1348, 142) or normal (GM 3349, 38) cultured fibroblasts for 1, 6, or 12 h resulted in the same type of damage and this was due to low protein levels. When the protein concentration of the conditioned media was increased with fetal bovine serum, the morphological integrity of the explants was maintained, demonstrating that there was no apparent difference between CF and normal fibroblast-secreted proteins in ability to induce mucus release. The ciliary inhibitory capacity of CF serum-derived or fibroblast-derived factor had been reported to require IgG for activity. However, addition of IgG to high molecular weight (VoP10) or low molecular weight (VeP10) secreted proteins had no apparent effect on stimulating secretion. In conclusion, it is possible that CF fibroblasts do not secrete a protein that has the mucostimulatory effect and thus these cells may not be suitable for studying the CF-related activity.

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Screening and Prenatal Diagnosis of Cystic Fibrosis: Introduction and Review

Hirschhorn¹

1982

Clinical Genetics

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Specificity of an Isolated Salivary Factor Material to Cystic Fibrosis

Abstract: Pediatr. Res. 15: 940-944 (1981) a-amylase cystic fibrosis factor cystic fibrosis specificity

Cited by 4 publications

References 12 publications

Effects of cystic fibrosis serum on calcium influx and secretion using isolated tracheal epithelial cells

Effects of cystic fibrosis serum on calcium influx and secretion using isolated tracheal epithelial cells

The effects of proteins secreted by fibroblasts from patients with cystic fibrosis on hamster tracheal explants

Screening and Prenatal Diagnosis of Cystic Fibrosis: Introduction and Review

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