HUMAN CLARA CELL 10-KDA PROTEIN IS THE COUNTERPART OF RABBIT UTEROGLOBIN

Human Clara cell 10-kDa protein has been suggested to be a counterpart of rabbit uteroglobin, an immunomodulatory and antiinflammatory secre tory protein. Since this human protein is not readily available in sub stantial quantity for detailed characterization of its biochemical, bi ological, and pharmacological properties, we sought to express it in E scherichia coli in order to study its structure-function relationship. However, bacterial overproduction of homodimeric proteins with interc hain disulfide bonds, such as Clara cell 10-kDa protein, was thought t o be impossible until we achieved expression of native uteroglobin (Mi ele, L., Cordella-Miele, E., and Mukherjee, A. B. (1990) J. Biol. Chem . 265, 6427-6435). Here, we report high level production of recombinan t native dimeric human Clara cell 10-kDa protein in E. coli and its ch aracterization. Recombinant human Clara cell 10-kDa protein forms its disulfide bonds within the bacterial cytoplasm. The purified protein p ossesses two of the most important activities characteristic of uterog lobin: (i) it is an excellent substrate of transglutaminase, and (ii) it is a potent inhibitor of porcine pancreatic and, more importantly, human synovial phospholipase A2. These results demonstrate that human Clara cell 10-kDa protein and rabbit uteroglobin have very similar bio chemical properties. Our data suggest that this protein may possess im munomodulatory and antiinflammatory activities of potential physiologi cal and pharmacological importance.