Publications

The glomerular mesangium is centrally involved in immune-mediated glomerulonephritis. The mesangial cell is a mesenchyme-derived multipotential vascular pericyte, which shares several properties with macrophages. Cultured, proliferating rat mesangial cells produce a factor, mesangial cell-derived thymocyte-activating factor (MC-TAF), which physicochemically and biologically closely resembles macrophage interleukin 1. MC-TAF is heat labile, of low m.w. (approximately 15,000), and adheres to anion exchangers. MC-TAF acts to augment lectin-induced thymocyte proliferation and enhances peripheral lymphocyte production of interleukin 2. These findings suggest that a mesangial cell cytokine may interact with the cellular immune system in an antigenically nonspecific fashion to modulate immune responses in glomerular disease.

A study to determine whether the bronchoconstriction induced by low concentration of sulfur dioxide in subjects with asthma decreases with repeated exposure was undertaken. Eight subjects with asthma performed 3 min of voluntary eucapnic hyperpnea with 0.5 ppm of SO2 in humidified filtered air three times at 30-min intervals and we measured specific airway resistance (SRaw) before and after each period of hyperpnea. Specific airway resistance increased significantly more after the first exposure to SO2 [(from 7.6 +/- 1.7 to 15.5 +/- 2.0 L x cm H2O/liter/sec (mean +/- SEM)] than after the second (from 8.1 +/- 1.3 to 10.8 +/- 1.6) or third (from 7.6 +/- 1.6 to 10.1 +/- 1.9) exposures (P less than 0.025). When seven subjects repeated hyperpnea with SO2 24 hr and 7 days later, SRaw increased as much as it had after the first exposure (from 8.2 +/- 2.5 to 15.5 +/- 4.5 at 24 hr and from 6.6 +/- 1.4 to 15.4 +/- 2.1 at 7 days). In four subjects repeated exposure to SO2 caused short-term inhibition of the bronchomotor response to SO2 but did not inhibit the bronchomotor response to histamine aerosol. It was concluded that repeated exposures to a low concentration of SO2 over a short period (on 1 day) can induce tolerance to the bronchomotor effects of SO2 in subjects with asthma. Tolerance to the bronchomotor effects of SO2 is not caused by decreased responsiveness of airway smooth muscle or a generalized decrease in the responsiveness of vagal reflex pathways since the bronchomotor response to histamine is preserved.

Complement localization was examined by direct immunoperoxidase procedures on frozen sections of baboon myocardium obtained 24 hours after ligation of the left anterior descending coronary artery. There was extensive localization of C3, C4, and C5 in most infarcted myocardial fibers; however, in these infarcted areas of myocardium, complement components were not found in myocytes immediately adjacent to either the endocardium or epicardium. Although C3, C4, and C5 were all present within the same myocardial fibers as assessed in adjacent serial sections, the light microscopic distribution of these components was dissimilar, i.e., C3 and C5 were present in both a granular and a diffuse pattern within myocytes, whereas C4 was always localized in a diffuse pattern. Complement components C3 and C5, but not C4, were also localized in the walls of small muscular arteries in infarcted myocardium. No complement was observed in myocardial fibers or blood vessels in normal baboon myocardium. Electron microscopic evaluation of C3 localization within infarcted myocardium indicated that C3 was associated with contractile elements of myocytes, as well as with membranes of myocyte nuclei, mitochondria, and sarcoplasmic reticulum. Within vascular smooth muscular cells, C3 was associated with myofilaments and mitochondrial membranes. Thus, the results of this study provide new information regarding the cellular and subcellular distribution of complement components in infarcted baboon myocardium. If this localization of C3, C4, and C5 is a result of their in situ activation within the ischemic myocardium, a variety of complement-derived phlogistic products would be expected to have been produced and to have effected, in part, the subsequent inflammatory response.