MURINE CD14 GENE-EXPRESSION IN-VIVO - EXTRAMYELOID SYNTHESIS AND REGULATION BY LIPOPOLYSACCHARIDE

A murine model system was used to study the distribution and regulatio n of CD14 gene expression in vivo. Western blot analysis failed to det ect CD14 in plasma from untreated CB6 (BALB/c x C57Bl6) mice, but show ed markedly increased levels of CD14 in plasma from mice treated with lipopolysaccharide (LPS). Plasma levels of CD14 increased in a time- a nd dose-dependent manner, reaching a maximum between 8 and 16 h. North ern blot analysis of total RNA extracted from mouse tissues revealed l ow, but significant, levels of CD14 mRNA in many tissues of untreated animals with the highest levels in uterus, adipose tissue, and lung. A fter intraperitoneal injection of LPS, induction of CD14 gene expressi on was detected in all organs examined with the extent of induction va rying between organs. Induction of CD14 mRNA was both time and dose de pendent. Maximum induction in the heart and lung was observed 2-4 h af ter injection of LPS, while liver and kidney showed maximal induction between 8 and 16 h. In situ hybridization showed that CD14 mRNA was ex pressed in myeloid cells in many tissues, and that expression in these cells was upregulated by LPS. Unexpectedly, CD14 mRNA was also detect ed in other cells within tissues, including epithelial cells, and expr ession in these cell types also was upregulated by LPS. Immunochemical analysis revealed that CD14 antigen colocalized to the cytoplasm of c ells expressing CD14 mRNA. These studies demonstrate that CD14 gene ex pression is not restricted to myeloid cells, and that the level of exp ression of CD14 is influenced by exposure to LPS.