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G Schmitz

Publications and source records attributed to G Schmitz.

294 records · Page 17Linked to original sources
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Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. I. Characterization of cellular lipid metabolism.

The effects of the slow Ca++ channel blocker, nifedipine, and ACAT inhibitor, octimibate, on the cholesterol metabolism of cholesterol-loaded macrophages were compared. We demonstrated that apolipoprotein A-I containing high density lipoproteins (HDL) bind to specific receptor sites on macrophages, are internalized, take up cholesterol, and are then released from the cells as native lipoproteins. The ACAT inhibitor enhances HDL receptor activity and promotes HDL-mediated cholesterol efflux from cultured mouse peritoneal macrophages. In contrast, the Ca++ antagonist increases acetyl LDL-mediated cholesterol influx, abolishes the increase in HDL binding induced by cholesterol accumulation, enhances apo E synthesis, and promotes cholesterol efflux by a mechanism independent of the presence of HDL in the surrounding medium. Concomitantly, a decrease in nucleoside transporter activity, an increase in intracellular ATP hydrolysis, adenosine and cyclic AMP concentration, and a stimulation of the activities of acid and neutral cholesteryl ester hydrolase and ACAT indicated that protein kinase A-catalyzed phosphorylation reactions might be involved in the increase in cholesterol efflux. The Ca++ antagonist-induced efflux occurred only with lysosomal-associated cholesterol, while the ACAT inhibitor acted on the formation of cytoplasmic lipid droplets. The secreted lipoprotein particles contained 68% unesterified cholesterol and 21% phospholipids, 8% esterified cholesterol, and 3% triglycerides. The phospholipid components were: 72% phosphatidylcholine, 22% sphingomyelin, and 6% phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine. We conclude that macrophages release cholesterol in two ways: 1) an HDL-mediated release of unesterified cholesterol increasing upon ACAT inhibition, and 2) an HDL-independent secretion of cholesterol which can be amplified by Ca++ antagonists.

Acetylation↗
PubMedDate not supplied

Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. II. Characterization of intracellular morphologic changes.

The effects of the slow Ca++ channel blocker, nifedipine, and ACAT inhibitor, octimibate, on cholesterol-loaded macrophages were compared at the ultrastructural level. The Ca++ antagonist induced the formation of membrane-surrounded "lamellar bodies" originating from lysosomes. The macrophages secreted these lamellar bodies, which were rich in phospholipids and cholesterol, into the culture medium even in the absence of cholesterol acceptors. In contrast, the ACAT inhibitor induced the formation of lamellar bodies originating from lipid droplets, which were also surrounded by membranes. There is strong evidence that these latter membranes were newly synthesized at the margin of the lipid droplets by the endoplasmic reticulum. The lamellar bodies descending from lipid droplets after ACAT inhibitor treatment were not secreted by the cells. They were stored in the cytoplasmic compartment in the absence of high density lipoproteins (HDL). When HDL were added to the medium, the lamellar bodies specifically interacted with endosomes containing the internalized HDL particles and disappeared concomitantly with an enhanced HDL-mediated cholesterol efflux. From the biochemical data in the accompanying article and the morphological data here, we conclude that macrophages release cholesterol by two major pathways: 1) an HDL-independent secretion of lamellar bodies containing cholesterol, which originate from lysosomes, and 2) an HDL-dependent release of cholesterol via the formation of lamellar bodies descending from lipid droplets, which intracellularly fuse with HDL-containing endosomes. The cholesterol-enriched HDL are then secreted as intact lipoproteins.

Animals↗
PubMedDate not supplied

Unusual musculoskeletal manifestations of Lyme disease.

We report on the imaging features of musculoskeletal abnormalities in a 52-year-old woman suffering from Lyme disease presenting with acrodermatitis chronica atrophicans (ACA). The patient developed recurrent attacks of migratory asymmetrical oligoarthritis, involving articular and peri-articular structures, including the metatarsophalageal (MTP) joints, scapular bone, thoracic spine, elbow, gluteal area, knee, ankle and metacarpophalangeal (MCP) joints. Six months after the first symptoms, Magnetic Resonance Imaging (MRI) showed bone marrow oedema within the proximal phalanx of the right fifth toe, adjacent to an ACA rash. A year after the onset of the disease, swelling at the right scapular region occurred, and MRI showed osseous, periosteal and soft tissue involvement of the superior margin of the right scapula and adjacent rib. On MRI of the spine, there was bone marrow infiltration with irregular delineation of the anterior corner of the thoracic vertebrae 4 to 6, corresponding to an osteoblastic bony lesion on radiographic examination. This case report is unique, because MRI documentation of bony abnormalities and periarticular soft tissue swelling, accompanying an attack of ACA has never been reported previously. Moreover, involvement of the osseous spine and the scapular bone have never been described in the radiological literature.

Acrodermatitis↗
PubMedDate not supplied

Monitoring of peripheral blood cytotoxic T-cells under fluvastatin treatment in renal transplant recipients.

Flow cytometric T-cell analysis is capable of adding valuable information for balancing immunosuppression in transplant recipients as it can take into account individual effects of immunosuppressive drugs on each patient as well as effects of other drugs which may modify the overall immunosuppression. Studies suggest that HMG-CoA-reductase-inhibitors (statins) reduce the frequency of organ rejection, although the precise mechanism of this effect is unknown. We therefore evaluated the effect of fluvastatin on size and activation of T-cell subpopulations and NK-cell activity in renal transplant recipients. At baseline, the population size of activated (HLA-DR+) T-cells was negatively correlated to serum HDL cholesterol suggesting an increased T-cell activation at low HDL levels. Fluvastatin treatment of a hypercholesterolemic group of patients for two months significantly decreased the LDL cholesterol. A longitudinal analysis revealed a relative increase in non-MHC restricted cytotoxic T-cells (CD3+/CD16+ or CD56+) over time which was significantly attenuated in fluvastatin treated patients but not in normocholesterolemic controls. Moreover, a relative decrease of activated MHC class I-restricted cytotoxic CD8+ T-cells was only observed upon fluvastatin treatment. NK-cell number and activity did not differ between groups. In summary, fluvastatin treatment of hypercholesterolemic renal transplant recipients is associated with a specific modulation of T-cells exerting cytotoxic effector functions.

Adult↗