NATURE OF DEFECT IN CYSTIC-FIBROSIS

Abstract

Sera and lymphocyte culture media derived from [human] cystic fibrosis(CF)-affected and carrier subjects contain ciliary dyskinesia factor (CDF) detected by a rabbit tracheal bioassay. CDF was also found 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 Ig[immunoglobulin]G. In all instances, CDF activity was eliminated by the addition of anti-IgG. A fraction with a MW between 1000 and 10,000 was isolated from CF sera and culture media which is inactive in the bioassay until IgG is added. This fraction behaves similar to the complement [C] derived anaphylatoxin C3a [fragment a of the 3rd C component]. Activity was found in sera from CF patients, and to a lesser extent in 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, the primary defect in CF may be the deficiency of an enzyme whose substrates include a family of membrane-active molecules.