Alpha-1-antitrypsin (AAT) and its stimulation in the liver of PiMZ phenotype individuals. A "recruitment-secretory block" ("R-SB") phenomenon.

PiMZ individuals in conditions of clinical stimulation show a peculiar immunohistochemical staining pattern for alpha-1-antitrypsin (AAT) in the liver: 1) the positivity involves large zones of parenchyma (up to 100% of hepatocytes); 2) in zone 2 and zone 3 hepatocytes the positivity appears in the form of crescents or rectilinear arrays along the sinusoids. This new pattern is designated type II, in contrast to type I which occurs in periportal hepatocytes in the form of inclusions spread over the whole cytoplasm. This peculiar staining pattern is associated with serum elevation of AAT and is considered to be an expression of liver reactivity. Type II positivity marks the hepatocytes which are newly recruited for the synthesis of AAT; owing to its defective export, the Z AAT is retained within the cell and detectable by immunohistochemistry. Thus this staining pattern is an expression of both recruitment for synthesis and block of secretion ("Recruitment-Secretory Block" "R-SB" phenomenon). In PiMZ individuals, the secretory block affects selectively and exclusively the Z fraction of AAT. At the EM level the vast majority of the retained protein is found in the RER, which represents the major and the earliest site of storage. Viewed in the framework of present knowledge of glycoprotein biosynthesis, the results of this study shed further light on the nature and cellular site of the Z AAT defect.