On the nature of the defect in cystic fibrosis

Sera and lymphocyte culture media derived from cystic fibrosis (CF)-affected and carrier subjects contain ciliary dyskinesia factor (CDF) detected by our rabbit tracheal bioassay. In addition, we also find CDF in fibroblast media from these same donors and in amniotic fluid cell media derived from CF carrier or affected fetuses. In these latter instances, the media were inactive in the bioassay, but became active when mixed with purified IgG. In all instances, CDF activity was eliminated by the addition of anti-IgG. We have separated a low molecular weight fraction, between 1,000 and 10,000 M.W., from CF sera and culture media which is inactive in the bioassay until IgG is added. Presumptive and indirect evidence indicates that this fraction behaves similarly to the complement derived anaphylatoxin C3a. In addition, we have found activity in sera from CF patients and, to a lesser extent, carriers that induces degranulation of cytochalasin-B-treated human polymorphonuclear leukocytes. Since this activity appears to be in a different molecular species from that containing CDF, we postulate that the primary defect in CF is the deficiency of an enzyme whose substrates include a family of membrane-active molecules.