Distribution and cellular origin of collagen VI during development and in cirrhosis

Collagen VI is a ubiquitous microfibrillar collagen that forms a network in most interstitial connective tissues, including soft organs and cartilage. The extracellular and intracellular distribution of collagen VI in human liver was studied by light and electron microscopy using the indirect immunoperoxidase method. In normal adult liver, collagen VI was seen mainly in portal spaces and formed a continuous layer in the sinusoids. Fetal liver contained more of collagen VI in the sinusoid than newborn and adult livers. In alcoholic fibrotic and cirrhotic livers, collagen VI antibodies intensely stained fibrous septa that invaded the lobule. Immunoelectron microscopy on normal liver showed that collagen VI antibodies labeled microfibrillar material and occasionally the surface of cells including hepatocytes. In both perinatal and fibrotic livers, electron-dense deposits were abundant in the space of Disse, intensely staining fibrils located around bundles of banded collagen. In both normal and fibrotic adult livers, collagen VI was abundant in the rough endoplasmic reticulum of Ito cells, while hepatocytes were constantly negative. In fetal livers, hepatocytes also contained collagen VI. These results suggest that collagen VI is a major constituent of the hepatic extracellular matrix. Furthermore, the cellular sources of collagen VI appear to be different in adult and developing livers.