Synthesis of stress proteins is increased in individuals with homozygous PiZZ alpha 1-antitrypsin deficiency and liver disease.

Individuals who are homozygous for the protease inhibitor phenotype Z (PiZ) genetic variant of alpha 1-antitrypsin (alpha 1-AT) have reduced plasma concentrations of alpha 1-AT, and are susceptible to premature development of pulmonary emphysema. A subset of this population develops chronic liver disease. The reduction in plasma concentrations of alpha 1-AT results from a selective defect in secretion as the abnormal PiZ alpha 1-AT protein accumulates within the cell.

Distinct and additive effects of elastase and endotoxin on expression of alpha 1 proteinase inhibitor in mononuclear phagocytes.

Expression of alpha 1 proteinase inhibitor (alpha 1-PI) in human mononuclear phagocytes may provide a local mechanism for inactivation of serine proteases at sites of tissue injury, thereby preventing incidental damage to surrounding tissue and allowing for orderly initiation of repair. We have previously shown that serine (neutrophilic or pancreatic) elastase and lipopolysaccharide (LPS) each mediate an increase in the expression of alpha 1-PI in human peripheral blood monocytes and bronchoalveolar macrophages. In this study we demonstrate that elastase and LPS have an additive positive regulatory effect on alpha 1-PI expression.

Elastase regulates the synthesis of its inhibitor, alpha 1-proteinase inhibitor, and exaggerates the defect in homozygous PiZZ alpha 1 PI deficiency.

The net balance of neutrophil elastase, an enzyme that degrades many components of the extracellular matrix, and its inhibitor, alpha-1-proteinase inhibitor (alpha 1 PI), is thought to be a critical determinant in the development of destructive lung disease, especially in individuals with homozygous alpha 1 PI deficiency. Synthesis and secretion of alpha 1 PI has been recently demonstrated in cells of mononuclear phagocyte lineage, including peripheral blood monocytes and tissue macrophages. In this study we show that alpha 1 PI gene expression in human monocytes and bronchoalveolar macrophages is affected by a novel mechanism, whereby elastase directly regulates the synthesis of its inhibitor.

Regulation of hepatic acute phase protein synthesis by products of interleukin 2 (IL 2)-stimulated human peripheral blood mononuclear cells.

Cancer patients injected with recombinant human IL 2 develop marked changes in serum concentrations of hepatic acute-phase proteins. To determine if this acute-phase response involves a change in the rate of hepatic protein synthesis and if it is due to a direct effect of IL 2 on hepatocytes, human hepatoma-derived hepatocytes (Hep-3B cells) were incubated in medium containing IL 2 or in culture supernatants from IL 2-activated human peripheral blood mononuclear cells (PBMNC). The rate of synthesis of two acute-phase proteins, complement protein factor B and albumin, was determined by the incorporation of a radiolabeled amino acid precursor into newly synthesized protein as measured by analytical gel electrophoresis of immunoprecipitates.

Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression.

The monokine, cachectin/tumor necrosis factor (TNF) differs from interleukin 1 (IL-1) in primary structure and in recognition by a distinct cellular receptor. It does, however, encode effector functions that are similar to those of IL-1 and characteristic of the host response to inflammation or tissue injury. Accordingly, we examined the possibility that recombinant-generated human TNF regulates hepatic acute-phase gene expression.

Neuropeptide-FMRFamide-like immunoreactivity in Drosophila: development and distribution.

Neuropeptide-FMRFamide-like immunoreactivity was characterized in the fruit fly, Drosophila melanogaster. In the adult central nervous system, a stereotypic pattern of immunoreactive cell bodies and immunoreactive nerve processes and varicosities was observed, indicating a neurochemical role for FMRFamide-like substance(s) in Drosophila. Localization of immunoreactivity in the central nervous system of early larval stage revealed that the majority of the prominent FMRFamide-like immunoreactive neurons were already differentiated.