A pleural surface membrane, which could be ablated from frozen human lungs with forceps, has been analyzed chemically. The surface membrane was found to consist primarily of collagen (Type I) and to contain only 2.3–8% elastin. The mechanical properties of this membrane should differ markedly from those of alveolar parenchyma, since the connective tissue of the parenchyma contains 32% elastin.
Three human basement membranes, glomerular basement membrane (GBM) from renal cortex, alveolar basement membrane (ABM) from lung parenchyma and trophoblast basement membrane (TBM) from the terminal villi of placenta have been isolated by sieving and sonication techniques. Canine GBM and ABM were also prepared. There were marked differences among the membranes from human tissues. Compared to GBM, TBM had very little collagen but contained high concentrations of charged amino acids. ABM was intermediate in composition between GBM and TBM and contained desmosine and isodesmosine indicative of the presence of elastin. Canine ABM (c-ABM) did not contain desmosine or isodesmosine. In the canine system an antigen was detected in ABM which was not present in GBM. The membrane preparations were analyzed for fibronectin content using a specific antiserum to fibronectin. This glycoprotein could not be detected in GBM whereas it was present in ABM in amounts up to 0.8% and in TBM in amounts as high as 7.2%. All the membranes induced the formation of precipitating antibodies in rabbits. Soluble material obtained from the membranes by alkali extraction, reduction of disulfide bonds, enzymatic digestion with elastase, plasmin or collagenase provided immunologically reactive fragments. These soluble fragments gave reactions of identity among the three basement membranes in immunodiffusion reactions in gels with antisera raised to all three BMs. The finding that plasmin digests basement membranes suggests that it may play a role in connective tissue remodeling. The fact that elastase degrades basement membranes provides an endogenous system for injury which may be triggered by infections.
Concentrations of α1-antitrypsin were measured in 80 specimens of amniotic fluid collected at various stages of pregnancy. Levels remained relatively unchanged throughout gestation, with a median concentration of 10.0 mg/100 ml at 12–24 weeks, 18.7 mg/100 ml at 34–37 weeks, and 16.2 mg/100 ml, after the 37th week. In three instances where the infant developed RDS, the median concentration was 12.4 mg/100 ml.
Amino acid analysis of human fetal lung elastin was undertaken in 49 instances of live-born neonates, ranging from 380 g to full term, and in 3 abortuses of 12-14 wk gestation. The data suggest that formation of the cross-linking agents, desmosine and isodesmosine, occurs early, between 14 and 22 wk. The ratio of neutral to charged amino acids remains low until the 36th wk when it attains adult levels. The composition of elastin was independent of sex and duration of survival. In three neonatal pulmonary diseases (respiratory distress syndrome, atelectasis, and hemorrhage) ratios were significantly lower than those found in nondiseased lungs. This may be a reflection of immaturity or may be a predisposing factor in neonatal lung disease. The latter hypothesis is attractive and receives indirect support from the association of a more polar elastin with other diseases, including adult emphysema and atheromatous aortic change.Our finding of relatively high polarity in elastin from human fetal lung is consistent with previous observations in a variety of fetal organs of other species.
A controlled, prospective study of 3 factors in asthmatic children was undertaken: immunoglobulin and enzyme inhibitor concentrations in the serum and bacterial flora of the nose and throat. Serum concentrations of immunoglobulins G, A, and M and α1-antitrypsin, and total trypsin inhibitory capacity were comparable in the asthmatic children and a control group. There was significantly more nasal colonization with Staphylococcus aureus among the asthmatic children than the control subjects, but this finding was not correlated with disease. β-hemolytic streptococci were not recovered, and gram-negative bacilli were rare. Pneumococci were present in 1 to 5 per cent, without significant difference between patients and control subjects. It was concluded that the asthmatic children and control subjects did not differ with regard to these 3 factors.
This paper describes a test for elastase which employs oxalic acid-solubilized elastin as the substrate. The test described is more sensitive than those using insoluble elastin-dye complexes and more specific than the recently introduced tests using synthetic peptide-esters. It can be used in the presence of other proteins, including serum, and is especially suited for the study of serum elastase inhibitors in health and disease.
Decreased serum elastase inhibitor concentrations were observed in 15 of 17 newborns with the respiratory distress syndrome. The mean concentration was 25 units of elastase inhibited per ml of seru...
NUMEROUS reports during the past 30 years support the thesis that biologically active factors present in normal adult tissue, growth-stimulating and growth-inhibiting substances, form a complex which regulates the growth of normal adult tissue. Upset of this balance may result in the unrestrained growth of cancer1–7. We have described the extraction by mild tryptic digestion of constituents of normal adult connective tissue (aorta, tendon, and skeletal muscle) which were growth-stimulating or growth-inhibitory to normal fibroblasts in tissue culture8. The effect on growth in vitro varied according to the conditions of extraction. Inhibitory extracts and crude precipitates from them further inhibited the growth in primary tissue culture of a series of human tumours from 75 to 100 per cent (refs. 9, 10).