THE GENE ENCODING VITAMIN-K-DEPENDENT ANTICOAGULANT PROTEIN-S IS EXPRESSED IN MULTIPLE RABBIT ORGANS AS DEMONSTRATED BY NORTHERN BLOTTING, IN-SITU HYBRIDIZATION, AND IMMUNOHISTOCHEMISTRY

Vitamin K-dependent protein S is an anticoagulant plasma protein that functions as a co-factor to activated protein C in the degradation of coagulation factors Va and VIIIa. We investigated the tissue/cellular distribution of protein S synthesis by Northern blotting, in situ hybr idization, and immunohistochemistry. Northern blotting together with i n situ hybridization, using specific oligodeoxynucleotide probes, demo nstrated protein S mRNA in liver, lung, testis, epididymis, ovary, ute rus, and brain. In the reproductive system, protein S mRNA was present in the cytoplasm of Leydig cells, interstitial cells of the ovary, ep ithelial cells of the epididymis, and in the endometrium, including en dometrial mucous glandular membrane in the myometrium. Bronchial epith elial cells and alveolar macrophages were positive in the respiratory system. In the central nervous system, pyramidal neurons in the cerebr al cortex and in the hippocampal region, and dentate fascia neurons ga ve strongly positive signals. Immunohistochemistry with monoclonal ant ibodies yielded a staining pattern that correlated well with results o f in situ hybridization. In conclusion, results from Northern blotting , in situ hybridization, and immunohistochemistry suggested that rabbi t protein S is expressed in several extrahepatic tissues. The presence of protein S transcripts in these fully differentiated cells suggests a cell type-specific gene expression which may be related to local an ticoagulation or to other as yet unknown protein S functions.