Demonstration of human leukocyte degranulation induced by sera from homozygotes and heterozygotes for cystic fibrosis.

The ability of epsilon-amino caproic acid (EACA)-treated normal serum and of cystic 
fibrosis (CF)-affected and carrier sera to promote the release of lysosomal 
enzymes from sensitized human polymorphonuclear leukocytes (PMN) was assessed through the 
measurement of beta- glucuronidase and myeloperoxidase activity after exposure of these 
cells to the various test sera. This study was initiated to 
extend the analogies between preciliary dyskinesia factor (pre-CDF), separated from the 
cell-free media of cultures derived from CF homozygous and heterozygous individuals, 
and C3a anaphylatoxin. The extent of lysosomal degranulation of human PMN 
exposed to fresh untreated sera of each of five controls, seven 
CF homozygotes, and eight heterozygotes, as expressed by the amount of 
beta-glucuronidase releases, was 7.84% (+/- 0.934) for control sera, 14.01% (+/- 
1.79) for CF-affected sera, and 10.61% (+/- 1.43) for heterozygous sera. 
The difference between CF homozygotes and control subjects is significant (P 
less than 0.0001), as is the difference between CF- affected and 
carrier individuals (0.001 less than P less than 0.005) and between 
control subjects and carriers (0.001 less than P less than 0.005), 
when beta-glucuronidase. However, the differences between control subjects and CF heterozygous 
individuals are not significant. Treatment of these sera with 1 M 
EACA gave values for beta-glucuronidase and myeloperoxidase release which are slightly 
reduced when compared with those obtained with fresh, untreated samples. EACA 
apparently reduces the activity of beta-glucuronidase released from PMN. Amicon filtration 
studies of these serum samples demonstrated that degranulating ability and the 
presence of cilicary dyskinesia, as assessed by rabbit tracheal bioassay, are 
not always associated. Therefore, the relationship between pre-CDF and the degranulator 
activity in native CF-affected and carrier sera is unclear, in part 
because of the limitations inherent in the test systems employed. 