muramidase and alpha-1-Antitrypsin-Deficiency

alpha 1-Antitrypsin (alpha 1-AT) is an acute phase plasma protein predominantly derived from the liver which inhibits neutrophil elastase. Previous studies have suggested that alpha 1-AT is also expressed in human enterocytes because alpha 1-AT mRNA could be detected in human jejunum by RNA blot analysis, and alpha 1-AT synthesis could be detected in a human intestinal adenocarcinoma cell line Caco2, which spontaneously differentiates into villous-like enterocytes in tissue culture. To definitively determine that the alpha 1-AT gene is expressed in human enterocytes in vivo, we examined tissue slices of human jejunum and ileum by in situ hybridization. The results demonstrate specific hybridization to enterocytes from the bases to the tips of the villi. Although there was no hybridization to enterocytes in most of the crypt epithelium, there was intense specific hybridization in one region of the crypt. Double-label immunohistochemical studies showed that alpha 1-AT and lysozyme co-localized to this region, indicating that it represented Paneth cells. Finally, there was a marked increase in hybridization to alpha 1-AT mRNA in villous enterocytes and Paneth cells in Crohn's disease. The results of this study provide definitive evidence that alpha 1-AT is expressed in human jejunal and ileal enterocytes in vivo, and show that alpha 1-AT is also a product of Paneth cells. Together with the results of other studies, these data raise the possibility that alpha 1-AT detected in fecal alpha 1-AT clearance assays for diagnosing protein-losing enteropathies is predominantly derived from sloughed enterocytes.

Topics: Adenocarcinoma; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Antisense Elements (Genetics); Colonic Neoplasms; Epithelial Cells; Epithelium; Fluorescent Antibody Technique; Gene Expression; Humans; Ileum; Immunohistochemistry; In Situ Hybridization; Jejunum; Liver; Muramidase; RNA, Messenger; Tumor Cells, Cultured

In recent years it has become known that proteolytic enzymes which are normally set free in pulmonary tissue can destroy the parenchyma unless they are adequately neutralized by enzyme inhibitors. Pulmonary emphysema caused by alpha 1-antitrypsin deficiency is an example of this. In the conducting airways as well, proteolytic activity occurs especially if there is infection. An enzyme inhibitor (LMI) has recently been discovered which is not present in the blood, but which is secreted by nasal and bronchial submucosal glands. The properties and the localization of LMI will be discussed, notably in the small airways. The consequences of a possible lack of this inhibitor will be discussed.

Topics: alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; alpha-Macroglobulins; Bronchi; Humans; Lung; Muramidase; Peptide Hydrolases; Phenotype; Protease Inhibitors; Pulmonary Alveoli; Pulmonary Emphysema

In a group of 115 children, originating from an area with industrial air pollution, a subgroups of 13 (11.3%) children was found with markedly decreased levels of alpha 1-antitrypsin (A 1-AT). Most children of the concerned subgroups were girls (10/64 - 18.5%), and only 3/61 (4.9%) were boys. In comparison with another group of 120 children, originating from an unpolluted area, only 2 (1.7%) of children showed decreased levels of A 1-AT. Significantly decreased serum levels of IgM and Lysozyme were simultaneously found in the hypo A 1-AT children, whereas IgG, IgA and total blood proteinemia did not differ from the controls. Increased morbidity, especially for respiratory diseases, was found in the group with the A 1-AT decreased below the level of 1.5 mg/ml, in comparison with the children of the same area without a decrease of A 1-AT. The lowest morbidity was stated in the control from non-polluted area. The decreased A 1-AT levels were restored to the normal values after half a year in most of the afflicted children, with the exception of two girls. Hypothesis is suggested that markedly decreased A 1-AT values could be caused by environmental influences. This acquired deficiency is reversible in contrast with the well known genetical deficiency.

Topics: Adolescent; Air Pollutants; alpha 1-Antitrypsin Deficiency; Blood Proteins; Child; Czechoslovakia; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Morbidity; Muramidase