Proliferation Of Intrinsic Cells Research Articles

Cigarette smoke causes rapid cell proliferation in small airways and associated pulmonary arteries

To determine whether smoke could directly affect the cells of the small airways and the small vessels, we exposed Sprague-Dawley rats to the whole smoke of 7 cigarettes/day for 1, 2, or 7 days. Three hours before the rats were killed, 5-bromo-2'-deoxyuridine (BrdU) was administered. Labeled nuclei were counted in histological sections stained with antibodies to BrdU. In smokers, pulmonary artery walls at the level of the membranous bronchioles (MB), respiratory bronchioles (RB), and alveolar ducts (AD) showed significant increases in labeled nuclei at all three times; increases in endothelial labeling were only present in vessels associated with AD. Significantly increased labeling was also seen in the epithelium and walls of MB and RB themselves at all time periods. However, there was no correlation between labeling indexes in matched pairs of airways and vessels. Smoke had no effect on the labeling of mesothelial and submesothelial cells. We conclude that cigarette smoke rapidly causes proliferation of intrinsic cells in the airways and small vessels; this effect may lead eventually to airway wall muscular hyperplasia and fibrosis (small airways disease) and to vascular changes associated with pulmonary hypertension. However, the lack of correlation between labeling indexes in the vessels and airways suggests that different mediators are involved at these two sites. At least over the time course of this experiment, smoke does not cause proliferation of mesothelial or submesothelial cells.

Glomerular macrophage proliferation in experimental immune complex nephritis

In immune complex nephritis, glomerular hypercellularity is known to result from the proliferation of intrinsic cells and from the infiltration of mononuclear cells, primarily macrophages. An immunohistochemical double-labeling procedure was used to determine whether macrophages were among the cells which may undergo mitosis within the glomerular tuft. The monoclonal antibody ED1 served as a macrophage marker; cells in the S-phase of mitosis were recognized by uptake of bromodeoxyuridine. Glomerular proliferation was studied in chronic serum sickness of LEW rats, an animal model of immune complex nephritis for which the relationship between immunopathology and pathophysiology has been well described. In normal glomeruli, resident mesangial macrophages accounted for an unexpectedly large proportion (≥one-third) of the total mitotic activity. In immune complex glomerulonephritis, the rate of glomerular macrophage proliferation increased rapidly just at the onset of proteinuria and remained high throughout the remaining course of disease. Glomerular macrophages from rats with proliferative nephritis also divided more vigorously than normal in short term culture in vitro, while persistently expressing abnormal surface marker phenotypes. The proliferation of mesangial macrophages appears to be a prominent feature of the normal process of glomerular cell renewal. In hypercellular glomeruli, vigorous local proliferation could greatly amplify the potential of macrophages to cause damage.