Biomedical subjects
Publications and source records attributed to J E Keri.
A case of purpura fulminans in a 44 year old woman infected with malaria is reported. The patient had laboratory findings consistent with disseminated intravascular coagulation and a severe eruption consisting of hemorrhagic bullae and crusts. This case is presented to elucidate another cutaneous manifestation of malaria.
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The production of collagen-degrading proteases by cultured neonatal rat microglia was examined using an immobilized fibronectin-gelatin matrix coupled to a fluorescent marker and by substrate gel analysis. When microglia were plated onto the surface of the matrix and incubated under resting (nonstimulated) conditions, a small but visible amount of immobilized matrix was degraded. Treatment with lipopolysaccharide (LPS) or interleukin-1 (IL-1) significantly increased the number of microglia demonstrating substrate degradation. Substrate-SDS polyacrylamide gel electrophoresis of samples of supernatants from untreated cultured microglia indicated the presence of a 72 and a 92 kD metalloproteinase with characteristics corresponding to collagenases. Supernatants from untreated astrocyte cultures were shown to have primarily a 72 kD metalloproteinase. Proteinase activity increased on stimulation of the microglia with LPS and IL-1 in a dose-dependent fashion. These results indicate that cultured microglia release active proteases capable of degrading the extracellular matrix in a localized region. The production of proteases by activated microglia may have important physiological and pathophysiological consequences within the restricted extracellular matrix of the CNS.
The production of interleukin-1 (IL-1) by cultured neonatal rat microglia was studied using the D10 cell assay. The results show that IL-1 was secreted in response to lipopolysaccharide (LPS) in a dose- and time-dependent fashion. IL-1 production was specific to microglia and was not induced in astrocytes. Indomethacin, which is known to modulate the release of IL-1 from monocytes, had no effect on LPS-stimulated microglia. Aging of the microglia from two weeks to 4 weeks in culture, however, reduced the release of IL-1 in response to LPS. Our data indicate that microglia are a major source of IL-1 and that the release of IL-1 depends on the presence of inflammatory mediators such as LPS and the age of the culture.
Cultured neonatal rat microglia were pretreated with varying doses of either purified interferon (IFN) alpha/beta or recombinant IFN gamma for 24 or 48 h and the following functional parameters examined; superoxide anion production, interleukin-1 secretion and chemotaxis. IFN gamma produced a marked increase in superoxide anion levels when PMA was used to initiate superoxide anion production but had no effect in OPZ-stimulated microglia. Treatment with IFN alpha/beta potentiated superoxide anion production in both PMA and OPZ-stimulated cells. Interleukin-1 activity was decreased by treatment with IFN gamma for 24 h while IFN alpha/beta increased IL-1 activity at 48 h. Removal of serum from the treatment media prevented the action of IFN alpha/beta on IL-1 production. Treatment with IFN alpha/beta or gamma decreased chemotaxis of microglia in response to zymosan activated serum. The data indicate that IFN gamma and alpha/beta can regulate microglial function and that this regulation may differ from that seen for other monocytically derived macrophages.
The production of interleukin-1 (IL-1) was examined in cultured CNS microglia obtained from trisomy 16 (Ts16) fetal mouse brain, a model system for studies relevant to Down syndrome (DS). When compared to microglia from their normal littermates, Ts16 microglia produced significantly higher levels of IL-1 activity both before and following stimulation with lipopolysaccharide (LPS). IL-1 release was stimulated by alpha/beta interferon (IFN) in the normal but not Ts16 microglial cultures. The overall level of IL-1 production in normal littermates, however, was still less than that seen in Ts16. Thus, microglia from Ts16 mice may function in an inappropriate manner and, if this abnormality occurs in vivo, may have wide ranging effects on a developing nervous system.