VITRONECTIN GENE-EXPRESSION IN-VIVO - EVIDENCE FOR EXTRAHEPATIC SYNTHESIS AND ACUTE-PHASE REGULATION

A competitive polymerase chain reaction (PCR) assay was developed to q uantitate vitronectin (Vn) mRNA in murine tissues using a synthetic RN A as an external standard. Although the liver contained the highest co ncentration of Vn mRNA, significant levels were also detected in the b rain (25-fold less) and in adipose tissue, heart, and skeletal muscle (100-fold less than liver). Lower concentrations also were detected in the lung, uterus, testis, and thymus, and little or no Vn mRNA could be detected in kidney, spleen, and blood. These results indicate that significant amounts of Vn mRNA are produced in extrahepatic organs. Th e regulation of Vn gene expression in vivo was studied in a murine mod el system in which acute systemic inflammation was induced by endotoxi n administration. Plasma Vn levels increased 2- to 3-fold within 16 h after endotoxin administration and remained elevated for up to 72 h. T his increase appeared to result from increased synthesis in the liver since the steady-state level of hepatic Vn mRNA increased 4-fold after endotoxin administration. Moreover, Vn mRNA levels in heart, lung, an d brain were not significantly increased by endotoxin. These results s uggest that Vn gene expression in vivo is regulated in a tissue-specif ic manner and identify Vn as a novel acute phase reactant.