CLONING AND CHARACTERIZATION OF A LUNG-SPECIFIC CDNA CORRESPONDING TOTHE GAMMA-CHAIN OF HEPATIC FIBRINOGEN

The gene (gamma FBG) encoding the fibrinogen gamma chain (gamma FBG) h as been shown to exhibit both tissue-specific and ubiquitous expressio n. To confirm the identity of the gamma FBG transcripts expressed in e xtrahepatic tissue, lung tissue was chosen as a model of extrahepatic gamma FBG gene expression. A ferret lung cDNA clone bank was construct ed in lambda gt11 and several positive plaques were isolated using cro ss-species hybridization with the rat gamma FBG cDNA. Sequence data of the longest clone, designated pFLG gamma 3, was compared at the nucle otide and deduced amino acid (aa) levels with sequences of gamma FBG f rom other species. The results indicated that the identity of the ferr et lung-specific gamma FBG cDNA to pig, rat, bovine and human gamma FB G cDNAs ranged from 78-88%; the similarity of the ferret lung-specific gamma FBG deduced aa sequence ranged from 84-88% across species. Cyst eine aa involved in intra- and inter-chain disulfide-bonded secondary and tertiary structure are absolutely conserved in ferret gamma FBG. T he putative cell-cell adhesion sites for both platelet alpha IIb beta 3 and intercellular adhesion molecule-1 receptor binding to ferret gam ma FBG are >90% similar to the corresponding sites in the human gamma FBG. The results of Northern hybridization indicated that the ferret l ung gamma FBG mRNA was equivalent in size to the liver gamma FBG mRNA; Southern hybridization suggested that ferret gamma FBG is a single-co py gene, as is the gamma FBG of other species. Lung-specific gamma FBG expression was localized to epithelial cells of the large and small a irways and chondrocytes by in situ RNA:RNA hybridization. The function al significance of gamma FBG expression in lung is not presently known . Since expression of FBG is up-regulated 2-10-fold in the liver durin g an inflammatory event, it is possible that lung-specific gamma FBG e xpression occurs predominantly during lung disease or injury.