LEKTI, a novel 15-domain type of human serine proteinase inhibitor

Proteinase inhibitors are important negative regulators of proteinase actio n in vivo. We have succeeded in isolating two previously unknown polypeptid es (HF6478 and HF7665) from human blood filtrate that are parts of a larger precursor protein containing two typical Kazal-type serine proteinase inhi bitor motifs. The entire precursor protein, as deduced from the nucleotide sequence of the cloned cDNA, exhibits 15 potential inhibitory domains, incl uding the Kazal-type domains, HF6478, HF7665, and 11 additional similar dom ains, An inhibitory effect of HF7665 on trypsin activity is demonstrated. B ecause all of the 13 HF6478- and HF7665-related domains share partial homol ogy to the typical Kazal-type domain but lack one of the three conserved di sulfide bonds, they may represent a novel type of serine proteinase inhibit or. The gene encoding the multidomain proteinase inhibitor, which we have t ermed LEKTI, was localized on human chromosome 5q31-32, As shown by reverse transcriptase-polymerase chain reaction and Northern blot analysis, it is expressed in the thymus, vaginal epithelium, Bartholin's glands, oral mucos a, tonsils, and the parathyroid glands. From these results, we assume that LEKTI may play a role in antiinflammatory and/or antimicrobial protection o f mucous epithelia.