Publications

Monocytic (MC) infiltration is a prominent feature of many forms of immune-mediated glomerulonephritis. Through the release of interleukin-1, (IL-1), monocyte/macrophages have been shown to induce the proliferation of mesangial cells and to stimulate the secretion of a glomerular basement membrane-degrading neutral proteinase. In addition, mesangial cells release a cytokine that expresses many of the biologic properties of monocyte IL-1, including stimulation of mesangial cell proliferation. Because many of the actions of IL-1 are mediated by the induction of prostanoid prostaglandin (PG) synthesis, the authors determined the effects of purified macrophage and mesangial IL-1 on the secretion of prostaglandin E (PGE), prostacyclin, and thromboxane. The results indicated that cycling MCs release primarily PGE in response to purified IL-1. The local release by either monocytes or mesangial cells of IL-1 during glomerular inflammation, with subsequent mesangial cell generation of vasodilatory PGE, may be responsible in part for the alterations in the glomerular microcirculation observed in these disorders.

Thrombospondin is a high-molecular-weight glycoprotein constituent of extracellular matrices of several cells in culture. Immunoreactive thrombospondin is also present within the normal human renal mesangium. To determine whether this thrombospondin could be a synthetic product of the intrinsic glomerular mesangial cells, we examined cultured human glomerular mesangial cells for the ability to synthesize and secrete thrombospondin. Well-characterized human mesangial cells were found to synthesize and secrete thrombospondin, as determined by specific immunostaining at the light- and electron-microscopic levels. Furthermore, metabolically labeled thrombospondin was immunoprecipitated from the conditioned medium of cultured cells. These studies suggest that the thrombospondin present within the normal mesangium is of intrinsic glomerular cell origin. Mesangial thrombospondin may be an important mediator of cellular function, particularly in disease states characterized by intrinsic glomerular cell proliferation.

X-ray holography offers the possibility of three-dimensional microscopy with resolution higher than that of the light microscope and with contrast based on x-ray edges. In principle, the method is especially advantageous for biological samples if x-rays in the wavelength region between the carbon and oxygen K edges are used. However, until now the achieved resolution has not exceeded that of the light microscope because of the poor coherence properties of the x-ray sources and the low resolution of the detectors that were available. With a recently developed x-ray source based on an undulator on an electron storage ring, and high resolution x-ray resist, a hologram has been recorded at about 400-angstrom resolution. The experiment utilized x-rays with wavelengths of 24.7 angstroms and required a 1-hour exposure of the pancreatic zymogen granules under study.