Cystic fibrosis: leakage of lysosomal enzymes and of alkaline phosphatase into the extracellular space.

Nine lysomal enzymes and alkaline phosphatase have been assayed with two different 
ultramicro techniques in the intra- and extracellular space of fibroblast cultures 
derived from the skin of cystic fibrosis patients, cystic fibrosis carriers, 
and normals controls, respectively. Evidence has been obtained for a multiple 
leakage of lysomal enzymes and of alkaline phosphatase into the medium 
of fibroblast cultures from cystic fibrosis patients and carriers. The situation 
is comparable to a certain extent, to that observed in I-cell-disease 
(mucolipidosis II). This multiple leakage results in the decrease of intracellular 
activity of several lysosomal enzymes in cultures from cystic fibrosis patients 
and carriers and due to the coordinate regulationof the synthesis of 
the "leaky enzymes" in an overshooting of the intracellular alkaline phosphatase 
activity in cultures from cystic fibrosis patients. It also explains the 
retarded catabolism of certain molecules, such as the Tamm-Horsfall glycoprotein, in 
cystic fibrosis cells. It is speculated that the basic defect in 
cystic fibrosis leads to abnormal recognition sites on lysosomal enzymes and 
on alkaline phosphatase, and in consequence to the leakage of those 
enzymes into the extracellular space. The present findings allow one to 
develop methods for the pre- and postnatal diagnosis of cystic fibrosis 
with cell cultures, and for the detection of cystic fibrosis carriers 
with the peripheral blood. 