TISSUE-SPECIFIC EXPRESSION OF THE GENE CODING FOR HUMAN CLARA CELL 10-KD PROTEIN, A PHOSPHOLIPASE-A(2)-INHIBITORY PROTEIN

Clara cell 10-kD protein (cc10kD), a secretory phospholipase A2 inhibi tor, is suggested to be the human counterpart of rabbit uteroglobin (U G). Because cc10kD is expressed constitutively at a very high level in the human respiratory epithelium, the 5' region of its gene may be us eful in achieving organ-specific expression of recombinant DNA in gene therapy of diseases such as cystic fibrosis. However, it is important to establish the tissue-specific expression of this gene before desig ning gene transfer experiments. Since the UG gene in the rabbit is exp ressed in many other organs besides the lung and the endometrium, we i nvestigated the organ and tissue specificity of human cc10kD gene expr ession using polymerase chain reaction, nucleotide sequence analysis, immunofluorescence, and Northern blotting. Our results indicate that, in addition to the lung, cc10kD is expressed in several nonrespiratory organs, with a distribution pattern very similar, if not identical, t o that of UG in the rabbit. These results underscore the necessity for more detailed analyses of the 5' region of the human cc10kD gene befo re its usefulness in gene therapy could be fully assessed. These data also suggest that cc10kD and UG may have similar physiological functio n(s).