Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells

Reelin regulates telencephalic and cerebellar lamination during mammalian d evelopment and is expressed in several structures of the adult brain; howev er, only traces of reelin were believed to be in peripheral tissues. Becaus e reelin structurally resembles extracellular matrix proteins, and because many of these proteins are expressed in blood, we hypothesized that reelin also might be detectable in the circulation. Reelin (420 kDa) and two reeli n-like immunoreactive bands (310 and 160 kDa) are expressed in serum and pl atelet-poor plasma of rats, mice, and humans, but these three bands were no t detectable in serum of homozygous reeler (rl/rl) mice. Reelin plasma leve ls in heterozygous (rl/+) mice were half of those in wild-type littermates. Western blotting and immunocytochemistry using antireelin mAbs indicated t hat reelin-like immunoreactivity was expressed in a subset of chromaffin ce lls within the rat adrenal medulla and in a subset of cells coexpressing cy -melanocyte-stimulating hormone within the pituitary pars intermedia. Howev er, surgical removal of adrenal or pituitary failed to decrease the amount of reelin (420-kDa band) expressed in serum. Adult liver expressed one-thir d of the reelin mRNA concentration expressed in adult mouse cerebral cortex . Full-length reelin protein was detectable in liver extracts in situ; acut ely isolated liver cells also secreted full-length reelin in vitro. Liver a ppears to be a prime candidate to produce and maintain the circulating reel in pool. It now becomes relevant to ask whether circulating reelin has a ph ysiologic role on one or more peripheral target tissues.