Fine structural observations of the liver in alpha-1-antitrypsin deficiency

Morphologic studies of liver tissue in individuals deficient in alpha-1-antitrypsin (alpha-1-AT) have established the presence of membrane-delimited deposits which are diastase resistant, perodic acid-Schiff positive, sialic acid deficient, and immunologically related to serum alpha-1-AT. The molecular basis for the accumulation alpha-1-AT-like substance in hepatocytes and the serum deficiency in alpha-1-AT patients is unknown. In an effort to gain insight into the membrane sites involved in the storage of the alpha-1-AT-like material, we examined liver biopsies by light and electron microscopy from 3 children with homozygous PiZZ deficiency and varying degrees of liver pathology. Contrary to the more widely held belief that accumulation occurs primarily in the rough endoplasmic reticulum, we find the earliest and greatest accumulation of alpha-1-AT-like material in smooth endoplasmic reticulum of hepatocytes. We have combined our ultrastructural observations with the current knowledge which is available concerning the structural properties of M-type and Z-type alpha-1-AT and have proposed a model which may explain the basis for the hepatic accumulation of alpha-1-AT-like material and the serum deficiency state in the PiZZ genotypes.