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At least 811 records · Page 45Linked to original sources
PubMed2004

Effect of green tea polyphenols on the genes with atherosclerotic potential.

The genomics of atherosclerosis can arise as a result of cross-talk between the genes coding for the LDL-receptor (LDL-R), LXR-alpha, PPARs (alpha, gamma), CD36 and C-myc because these genes control lipid metabolism, cytokine production and cellular activity within the arterial wall. The effect of green tea polyphenols (GTPs) upon such genomics revealed their ability to down-regulate genes coding for PPAR-gamma, CD36, LXR-alpha, C-myc coupled with up-regulation of genes coding for LDL-R and PPAR-alpha at the transcriptional level. Based upon these results, it is proposed that GTPs have the inherent capacity to inhibit the development of atherosclerotic lesions.

Arteriosclerosis↗
PubMed2002

Biliary anionic peptide fraction and apoA-I regulate intestinal cholesterol uptake.

Evidence is now in favor of protein-facilitated mechanisms for the intestinal cholesterol absorption. Here we report that the unesterified cholesterol uptake by rat jejunal brush border membrane vesicles (BBMVs) is efficient, saturable, and protein-mediated. The human apolipoproteins biliary anionic peptide factor (APF) and A-I (apoA-I) up-regulate micellar cholesterol uptake in a dose-dependent manner, but for all tested concentrations (0.1-20 microM), the lipid-free APF was more efficient than apoA-I. This uptake stimulation was suppressed after addition of Pabs directed to the external lipid-binding domain of the CLA-1/SR-BI and reduced by Pabs directed to the external loop of CD36. Thus, CLA-1/SR-BI and to a lesser extent CD36 are involved in the regulation of intestinal cholesterol uptake. APF, the main protein bound to biliary lipids, is likely one of their physiological effectors. As APF is an unesterified cholesterol carrier, it could facilitate the intestinal absorption of biliary cholesterol.

Animals↗
PubMed1994

Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages.

Monocyte/macrophages adhere to cells (lymphocytes, vascular endothelial and other cell types) and to extracellular matrix components (fibronectin and laminin) by using specific cell surface adhesive structures. In the present study we have analyzed expression of integrins, immunoglobulin (Ig)-related, selectins, and other adhesion molecules on blood monocytes, in vitro differentiated macrophages (ivMs), and alveolar macrophages (AMs), obtained from healthy nonsmokers by bronchoalveolar lavage (BAL). We have also investigated expression of adhesion molecules on myelomonocytic cell lines HL-60, THP-1, KG-1, and U937 before and after tetradecanoyl phorbol acetate (TPA)-induced differentiation. With regard to the integrin family, monocytes expressed beta 1 (CD29), alpha 4, alpha 5, alpha 6, beta 2 (CD18), CD11a, CD11b, and CD11c subunits, but not alpha V (CD51). Some reactivity with mAbs against the platelet antigens CD41b (IIb) and CD61 (beta 3) was detected. The Ig-related molecules CD54 (ICAM-1), ICAM-2, and CD58 (LFA-3) were expressed, as well as L-selectin and the carbohydrate ligands Le(x) (CD15) and sialyl Le(x). Immunolabeling for the structurally unrelated molecules CD44 and CD36 was strongly positive. In comparison to monocytes, AMs showed much lower expression of alpha 4, alpha 6, beta 2, CD11a, CD11b, L-selectin, Le(x), and sialyl Le(x). Moreover, ICAM-2 and CD36 were practically absent whereas expression of alpha 3, but not of CD11c, was higher. Similar results were obtained with ivMs. All four myelomonocytic cell lines showed down-regulation of alpha 4 and up-regulation of CD11c after TPA treatment. These findings indicate that maturation of monocytes into macrophages is accompanied by characteristic changes in adhesion molecule expression. The particular array of adhesion molecules on monocytes and macrophages may account for differences in the functional properties of these cells.

Antigens, CD↗
PubMed1993

Binding of sulfosuccinimidyl fatty acids to adipocyte membrane proteins: isolation and amino-terminal sequence of an 88-kD protein implicated in transport of long-chain fatty acids.

We recently reported (Harmon et al., J. Membrane Biol. 124:261-268, 1991) that sulfo-N-succinimidyl derivatives of long-chain fatty acids (SS-FA) specifically inhibited transport of oleate by rat adipocytes. These compounds bound to an 85-90 kD membrane protein which was also labeled by another inhibitor of FA transport [3H]DIDS (4,4'-diisothiocyanostilbene-2-2'-sulfonate). These results indicated that the protein was a strong candidate as the transporter for long-chain fatty acids. In this report we determined that the apparent size of the protein is 88 kD and its isoelectric point is 6.9. We used [3H]SS-oleate (SSO), which specifically labels the 88-kD protein, to isolate it from rat adipocyte plasma membranes. Identification of 15 amino acids at the N-terminus region revealed strong sequence homology with two previously described membrane glycoproteins: CD36, a ubiquitous protein originally identified in platelets and PAS IV, a protein that is enriched in the apical membranes of lipid-secreting mammary cells during lactation. Antibody against PAS IV cross-reacted with the adipocyte protein. This, together with the N-terminal sequence homology, suggested that the adipocyte protein belongs to a family of related intrinsic membrane proteins which include CD36 and PAS IV.

Adipose Tissue↗
PubMed2006

Increased gene expression of scavenger receptors and proinflammatory markers in peripheral blood mononuclear cells of hyperlipidemic males.

Interactions between peripheral blood mononuclear cells (PBMCs) and those within plaques are suggested to be pathophysiologically relevant to lipid-induced arteriosclerosis. In this study, gene expressions of scavenger receptors (CD36, CD68), LPS receptor (CD14), proinflammatory (tumor necrosis factor alpha [TNFalpha], CD40, interleukin-1 beta [IL-1beta]) and oxidative stress-related (manganese superoxide dismutase [MnSOD]) markers were analyzed in PBMCs of clinically asymptomatic males with classical proatherogenic risk factors such as smoking and/or hyperlipidemia. PBMCs were isolated from venous blood of normolipidemic non-smokers (n = 10) and smokers (n = 8), and hyperlipidemic non-smokers (n = 9) and smokers (n = 8). RNA from PBMCs was used for PCR analyses. Plasma concentrations of oxidized low-density lipoproteins (oxLDL) were measured by ELISA. The gene expressions of CD36, CD68, CD40, TNFalpha, and MnSOD were significantly higher in PBMCs of hyperlipidemics than in normolipidemics, irrespective of whether they were smoking or not. The individual expression of these genes showed significant positive correlations with each other but also with serum cholesterol or plasma oxLDL concentrations. The higher expressions of scavenger receptors, proinflammatory and oxidative stress-related genes of PBMCs are suggested to result mainly from hyperlipidemia and the accompanied increase of oxLDL concentrations.

Adult↗
PubMed2005

The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospondin.

BACKGROUND: Tumour growth is dependent on angiogenesis. Antiangiogenic chemotherapy, i.e. continuous or metronomic low-dose chemotherapy, is a method for administrating cytostatics at a low and well-tolerated concentration without prolonged breaks. The target is the genetically stable endothelial cells playing a pivotal role in angiogenesis within the tumour. Different mediators could mediate the antiangiogenic effect of metronomic chemotherapy. One of these mediators could be thrombospondin (TSP). TSP is a potent inhibitor of angiogenesis and might therefore be important in controlling tumour growth. This study was designed to evaluate the effects of low-dose continuous or moderate-dose bolus chemotherapy on tumour growth and on tumour expression of TSP. MATERIALS AND METHODS: Rats bearing a malignant prostate tumour (Dunning AT-1) not expressing TSP were treated systemically with cyclophosphamide, doxorubicin or paclitaxel and the combination of cyclophosphamide and doxorubicin. Tumour growth and body weight were measured during the treatment. CD36, one of TSP's main receptors, was also analysed. The expression pattern of TSP-1, TSP-2 and CD36 was investigated using immunohistochemistry and Western blot analyses. Q-PCR was used to analyse TSP-1 mRNA expression. RESULTS: Low-dose cyclophosphamide and paclitaxel re-induced the expression of TSP in the tumours. However, following a bolus dose of doxorubicin, tumours showed no expression of TSP. Both cyclophosphamide and doxorubicin treatments decreased the tumour weight by more than 60% compared with vehicle controls. When cyclophosphamide and doxorubicin were combined the tumour weight was reduced by 47%, while paclitaxel reduced the tumour weight by 18% compared to the vehicle controls. CONCLUSIONS: Systemic low-dose continuous treatment of a rat prostate cancer model with cyclophosphamide and paclitaxel induced the expression of TSP in tumour tissue and inhibited tumour growth. These findings support the hypothesis that the anti-tumour effect of low-dose metronomic chemotherapy, at least with certain chemotherapeutics, is partly mediated by induction of endogenous antiangiogenic factors.

Animals↗
PubMed2004

Neutrophils infiltrating ultraviolet B-irradiated normal human skin display high IL-10 expression.

Exposure to an erythemal dose of ultraviolet B (UVB) is known to induce interleukin (IL-10) expression in human skin. It is generally believed that this IL-10 is predominantly expressed by CD11b+ HLA-DR+ macrophages that infiltrate the UVB-exposed skin. This cytokine is presumed to contribute to the immunosuppressive effects of UVB by inhibiting cell-mediated immune responses. We recently demonstrated that neutrophils, which also invade UVB-irradiated skin, express CD11b and HLA-DR as well. In addition, we showed that the presence of these neutrophils affects T-cell responses in primary T-cell cultures derived from UVB-exposed skin. Since neutrophils invade UVB-exposed skin and, like macrophages, express CD11b and HLA-DR, we sought to determine whether neutrophils represent another source of IL-10. Skin biopsies were obtained from four healthy volunteers before and 2 days after exposure to four minimal erythema doses of UVB. A series of immunohistochemical double-staining procedures using the following markers was performed: IL-10, CD11b, HLA-DR, CD36, neutrophil elastase, and CD66b. As expected IL-10 could be detected in CD11b+ HLA-DR+ CD36+ macrophages in the epidermis and dermis of UVB-exposed skin. Surprisingly, the majority of the abundant IL-10 expression was found in CD11b+ HLA-DR+ elastase+ CD66b+ neutrophils. Cytospin preparations from dermal cell suspensions confirmed the IL-10 expression by neutrophils displaying characteristic multilobular nuclei. Thus, neutrophils in UVB-exposed skin express IL-10 and should be recognized as active coplayers in the creation of the UVB-induced immunosuppressive microenvironment.

Dermis↗
PubMed2006

Varied expression of functionally important genes of RPE and choroid in the macula and in the periphery of normal human eyes.

BACKGROUND: Topographic differences in RPE and choroid between macular and peripheral areas of the eye may predispose to morphologic and cell survival changes with aging. An understanding of the molecular events that distinguish RPE and choroid by their spatial location could give hints for the identification of survival factors and the development of new therapeutic approaches. To determine the mRNA expression of functionally important genes in RPE and choroid of morphologically normal human eyes, tissue patches were dissected from the macula and peripheral locations. METHODS: The mRNA levels of 29 genes with known functions or expression in the RPE/choroid were quantified in these sections by real time RT-PCR. Variations in the mRNA expression were determined due to differences in the mean normalized expression (MNE) between different peripheral locations, left and right eye of the same donor, and eyes of different donors. RESULTS: In the macula, the lysosomal enzyme cathepsin D (1.27E+00+/-1.54E-01) and the MERTK ligand Gas6 (1.08E+00+/-1.60E-01) had the highest MNE, whereas the apoptosis inducer Fas-Ligand (1.41E-04+/-6.46E-05) and the ROS internalization receptor CD36 (2.15E-04+/-1.11E-05) demonstrated the lowest expression. Interestingly, the PEDF expression (1.80E-01+/-4.56E-02) was 10 times higher than the VEGF expression (1.84E-02+/-2.46E-03) in the macular area. For most of the analyzed genes (52%, e.g. MERTK, integrin alphaV and beta5, RPE65, tyrosinase, VEGF) there was equal gene expression in the macula and in the periphery. For 31% of the genes (e.g. CD36, MAP1B) there was higher expression in the macula and for 17% of the genes (e.g. 11-cis RDH, VEGF-R2, PEDF) there was higher expression in the periphery. CONCLUSIONS: Whereas most of the analyzed genes expressed in RPE and choroid had equal mRNA expression levels in the macula and the periphery with donor dependent variations, there are important exceptions in genes that are involved in the maintenance of a specific vascular status in the macula (PEDF, VEGF and VEGR-R2) and in the recycling of rod outer segments (11-cis RDH). Applying this technique to the gene expression analysis of patients with AMD could identify those genes that are involved in molding of the disease.

Aged↗
PubMed2005

Leptin down-regulates peroxisome proliferator-activated receptor gamma (PPAR-gamma) mRNA levels in primary human monocyte-derived macrophages.

Increased leptin levels are associated with cardiovascular disease in obesity although the mechanism is unknown. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a key regulator of macrophage lipid metabolism and its activation by thiazolidinediones protects against atherosclerosis. The aim of this study was to assess the effects of human recombinant leptin on PPARgamma mRNA levels in primary human macrophages and macrophage-derived foam cells. Leptin treatment (100 ng/ml) for 24 h caused a 41% reduction (p < 0.01) in PPARgamma transcript levels in human-derived macrophages. This fall was accompanied by a reduction in the mRNA expression of carnitine palmitoyltransferase (CPT-I) (36%, p < 0.05) and ABCA1 (62%, p < 0.05), whereas CD36 mRNA reduction (34%) was not significant. In macrophage-derived foam cells, leptin at 20 ng/ml reduced PPARgamma mRNA levels by 33% (p < 0.01) and CPT-I by 27% (p < 0.05). At this concentration, leptin did not modify the expression of either ABCA1 or CD36. In agreement with these results, intracellular cholesterol ester accumulation was not altered in macrophage-derived foam cells by leptin at 20 ng/ml. We propose that the reduction in PPARgamma expression in both macrophages and foam cells may be one of the factors linking high leptin levels and cardiovascular disease.

ATP Binding Cassette Transporter 1↗
PubMedDate not supplied

Primary culture of human lung microvessel endothelial cells: a useful in vitro model for studying Plasmodium falciparum-infected erythrocyte cytoadherence.

In the past, several cell lines have been used as in vitro models for studying cytoadherence, which refers to the specific binding of Plasmodium falciparum-parasitized red blood cells (PRBC) to host endothelium of microvessels. These models include: (a) human cells, including human umbilical vein endothelial cells (HUVEC), C32 amelanotic melanoma cells and monocytes; (b) non-human cells transfected with human genes, including COS and CHO cells; and (c) purified candidate receptor molecules. However, endothelial cells from malaria target organs are rarely investigated. In this study, we describe the efficient isolation and characterization of human lung endothelial cells (HLEC). This is the first in vitro study of P. falciparum PRBC cytoadherence to human lung endothelium, one of the target organs during severe malaria. The endothelial nature of the HLEC lines was confirmed by the presence of the von Willebrand factor, anti-human platelet endothelial adhesion molecule-1 and E-selectin antigens as specific endothelial markers. After exposure of HLEC to human cytokines, FACScan analysis indicated the coexpression of PRBC receptors CD36, intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1). The laboratory-adapted P. falciparum strains adhered specifically in vitro to these HLEC. The binding of PRBC could be inhibited with variable efficiency by various monoclonal antibodies (anti-CD36 > anti-ICAM-1 > anti-VCAM-1 > anti-E-selectin). Target organ specific cell lines such as HLEC expressing a variety of potential P. falciparum PRBC cytoadherence receptors may provide in vitro systems for studying the pathophysiology of severe malaria and identifying new therapeutic agents designed to directly block adhesive events involved in severe malaria.

Animals↗
PubMed2005

3'UTR/T polymorphism of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with modified anti-platelet activity of atorvastatin in hypercholesterolemic subjects.

Oxidized-low density lipoproteins (ox-LDL) and the specific receptor LOX-1 are involved in atherogenesis and atherothrombosis. LOX-1 downregulation is associated with the anti-platelet action of atorvastatin. 3'UTR/T LOX-1 polymorphism has been associated with increased risk of coronary artery disease. This study was planned to determine whether LOX-1 genetic variations could affect anti-platelet action of atorvastatin. We studied by platelet P-selectin (P-sel), CD36 and LOX-1 expression (cytofluorimetric detection) whether differences in cellular activation could be suitable in 109 3'UTR/T carriers out of 201 hypercholesterolemic subjects treated with atorvastatin 20mg/day. Hyperactivated platelets (P-sel in resting cells and % variation upon thrombin activation, p<0.001) were detected at baseline in patients without significant differences between T or C carriers. P-sel and platelet-associated ox-LDL, were significantly decreased (all p<0.001) in C carriers after one week of treatment before LDL reduction. In 3'UTR/T carriers P-sel was reduced (p<0.01) after 6 weeks of treatment according to LDL and ox-LDL reduction. In 3'UTR/T carriers atorvastatin reduced platelet activity by LDL and ox-LDL lowering and not by rapid CD36 and LOX-1 downregulation as in C carriers. Such data suggest that in T carriers LDL lowering is needed to achieve anti-platelet action.

Adult↗
PubMed2006

Effects of rosiglitazone and atorvastatin on the expression of genes that control cholesterol homeostasis in differentiating monocytes.

We studied the effects of 5 microM atorvastatin, 2 microM rosiglitazone and their combination on intracellular cholesterol levels and on the expression of genes controlling cholesterol trafficking in human monocytes during their differentiation into macrophages. Our results show that treatment with rosiglitazone caused an increase in CD36 mRNA and protein levels (2.7- and 2.9-fold, P<0.001), but significantly induced the expression of most genes related to cholesterol efflux: ABCA1 mRNA (23%, P<0.05) and protein (2.4-fold, P<0.05), apo E protein (2.4-fold, P<0.05), caveolin-1 mRNA (2.6-fold, P<0.001) and SR-BI mRNA (1.9-fold, P<0.001) and protein (3-fold, P<0.01). As a consequence, rosiglitazone treatment reduced intracellular free cholesterol levels by 22% (P<0.01). Treatment with 5 microM atorvastatin caused the opposite effect on the expression of cholesterol efflux-related genes, which was generally reduced: ABCA1 mRNA (71%, P<0.05), apo E mRNA (46%, P<0.001) and protein (5.6-fold, P<0.001), and CYP27 mRNA (15%, P<0.05). Despite these reductions, intracellular total and free cholesterol levels were also reduced by 30% (P<0.01), an effect that can be attributed to the inhibition of de novo cholesterol synthesis by the statins. The combination of rosiglitazone with atorvastatin attenuated CD36 induction, and caused reductions similar to those caused by the statin alone on the expression of genes involved in cholesterol efflux and on intracellular cholesterol levels.

Atorvastatin↗
PubMed2005

Anti-inflammatory effects of UV-irradiated lymphocytes: induction of IL-1Ra upon phagocytosis by monocyte/macrophages.

One of the mechanisms proposed to explain immunomodulatory actions of ultraviolet light (UV) is production of endogenous anti-inflammatory cytokines. The purpose of the present study is to evaluate how UV light affects the production of IL-10 and IL-1Ra and to provide insight as to the role of phagocytosis of apoptotic lymphocytes in this process. Cytokine production was evaluated in a coculture system consisting in UV-treated lymphocytes in the presence of autologous PBMC. The impact of phagocytosis was tested by two blocking agents cytochalasin E and anti-CD36 mAb. The apoptotic process affecting irradiated lymphocytes was progressive, culminating at 48 h. To achieve significant cytokine production, irradiated lymphocytes were incubated overnight at 37 degrees C. Coculture of apoptotic lymphocytes with autologous PBMC resulted in a significant increase of IL-1Ra mRNA (+340%; P = 0.001) and protein (+72%; P = 0.001) production. This synthesis was blocked by cytochalasin E but upregulated by CD36 receptor cross-linking. Our study shows that UV light induces lymphocyte apoptosis followed by its phagocytosis by monocyte/macrophages, a step that preferentially activates IL-1Ra.

Apoptosis↗
PubMed2006

Evidence for downregulation of erythropoietin receptor in bone marrow erythroid cells of patients with chronic idiopathic neutropenia.

OBJECTIVE: The aim of this study is to probe the mechanisms underlying anemia in patients with chronic idiopathic neutropenia (CIN) by evaluating parameters of bone marrow (BM) erythropoiesis. PATIENTS AND METHODS: Ten CIN patients fulfilling the criteria of anemia of chronic disease, 27 nonanemic CIN patients, and 30 healthy volunteers were enrolled in the study. Reserves and survival characteristics of BM erythroid cells were evaluated using flow cytometry and clonogenic assays. Serum erythropoietin (EPO) was measured with ELISA. Expression of EPO receptors (EPORs) on BM erythroid cells was evaluated by flow cytometry and reverse-transcription polymerase chain reaction. RESULTS: CIN patients display defective erythropoiesis in addition to previously reported impaired granulopoiesis. Patients have low number of CD34(+)/CD71(+) progenitor and CD36(-)/ Glycophorin A(+) (GlycoA(+)) precursor BM cells, and increased proportion of apoptotic cells within the CD34(+)/CD71(+) and CD36(+)/GlycoA(+) compartments. Burst-forming units erythroid (BFU-Es) in BM mononuclear or purified CD34(+) cells were significantly reduced in the patients. Patient BFU-Es increased significantly following in vitro treatment with tumor necrosis factor-alpha (TNF-alpha) and/or interferon gamma (IFN-gamma)-neutralizing antibodies. Local TNF-alpha and IFN-gamma production was higher in anemic than in nonanemic patients. EPO production was appropriate in the patients, but EPOR expression was significantly reduced in patient GlycoA(+) cells, especially in anemic patients. CONCLUSION: Impaired BM erythropoiesis in CIN patients is probably the result of increased local production of TNF-alpha and IFN-gamma that induce apoptosis, cell growth inhibition, and downregulation of EPOR expression on erythroid cells. We suggest that anemia in CIN patients displays overlapping pathophysiologic features with anemia of chronic disease.

Adult↗
PubMed2004

Evaluation of Cytokeratin 7 as an accurate intracellular marker with which to assess the purity of human placental villous trophoblast cells by flow cytometry.

Villous trophoblast cells (TC) obtained from first trimester and term human placentae after trypsin/Percoll gradient isolation were immunodepleted of contaminant cells. The level of purity was assessed by the intracellular expression of the pan trophoblast marker cytokeratin-7 (CK7) and comparisons were made with the GB25 trophoblast-specific (cytotrophoblast+syncytiotrophoblast) cell surface marker. The presence of contaminating cells was traced with intracellular vimentin, or cell surface CD2, CD36, and CD163 markers and evaluated by flow cytometric analysis. The pattern of CK7 expression by trophoblast cells was also analyzed by immunofluorescence microscopy. Most batches of TC from first trimester or term placentae (92+/-3% and 96+/-2%, respectively) showed a high percentage of CK7 expressing cells, with less than 2% contaminating vimentin positive cells. In some batches of TC with a lower percentage (65+/-4%) of CK7-expressing cells, no vimentin was found, but a low percentage of CD36-expressing cells was evidenced, with no presence of CD2, and/or CD163-expressing cells. The intracellular CK7 signal correlated significantly with that of GB25 (p<0.05) cell surface expression in TC of term placentae. The choriocarcinoma BeWo and Jar cell lines also showed high levels (>92%) of CK7-expressing cells. Conversely, the control U87 astrocytoma cell line showed a high percentage (>90%) of vimentin but no CK7-expressing cells. These results provide evidence that the mutually exclusive pattern of intracellular CK7/vimentin expression of human TC can be used for evaluation by flow cytometry of the purity of primary human trophoblast cells.

Antigens, CD↗
PubMed2004

Severe functional alterations in vitro in CD34(+) cell subpopulations from patients with chronic myeloid leukemia.

Chronic myeloid leukemia (CML) arises from the malignant transformation of a hematopoietic stem cell (HSC) that gives rise to functionally defective progeny, including primitive and relatively mature progenitor cells (HPC). Both HSC and HPC are comprised within the population of CD34(+) cells, normally present in bone marrow (BM). In the present study, we have separated two different subpopulations of CD34(+) cells from CML marrow: Population I, enriched for CD34(+) Lin(-) cells; and Population II, enriched for CD34(+) CD36(-) CD38(-) CD45RA(-) Lin(-) cells, and assessed their progenitor cell content as well as their capacity to proliferate and expand in response to a combination of hematopoietic cytokines in serum- and stroma-free long-term liquid cultures. The absolute cell numbers recovered in Population I from normal and CML samples were similar; in contrast, we found that Population II from CML was amplified four-fold, as compared to normal. In spite of this latter observation, no significant differences were observed in terms of the absolute number of CFC when comparing Populations I and II from CML patients and normal subjects. Interestingly, the proliferation and expansion potentials of CML cells were clearly deficient as compared to their normal counterparts. Indeed, in cultures of Population I cells the maximum fold increase in total and progenitor cell numbers corresponded to 30 and 8%, respectively, of those observed in cultures of normal marrow-derived Population I cells. Such functional deficiencies were even more evident in Population II cells in which the maximum fold increase in total and progenitor cell numbers corresponded to 3 and 0.5%, respectively, of the levels found in cultures of Population II cells from normal marrow. The present study demonstrates that bone marrow-derived CD34(+) cells from CML patients possess functional abnormalities, clearly evident in the in vitro system used by us. Among the two CML subpopulations studied here, the more immature one (Population II; enriched for CD34(+) CD36(-) CD38(-) CD45RA(-) Lin(-) cells) was the one that showed the most severe abnormalities, as compared to its relatively more mature counterpart (Population I; enriched for CD34(+) Lin(-) cells).

Adolescent↗
PubMed2004

Cell membrane proteins and quasispecies compartmentalization of CSF and plasma HIV-1 from aids patients with neurological disorders.

Cell membrane protein (CMP) profile of HIV-1 from cerebrospinal fluid (CSF) and plasma of five AIDS patients with neurologic disorders was analyzed and compared with viral quasispecies composition in these body compartments. To this aim, paired CSF and plasma samples from AIDS subjects with HIV-related neurological diseases (three HIV-1 encephalopaty (HIVE) and two primary CNS lymphoma (PCNSL)) underwent immobilized antibody capture (IAC) assay to determine the profile of CMP acquired by HIV-1. The considered CMPs were CD45RO, CD26, CD36, glut-R, N-CAM, VCAM-1, ELAM-1, CD44 and CD58, representing lymphomonocyte, neuronal and adhesion molecules. Cloning and sequencing of env and gag regions was performed to predict coreceptor usage and to analyze quasispecies compartmentalization. The results indicated that CD44 and CD58 were the most represented molecules on HIV-1 from CSF, whereas CD36 was the most abundant molecule on plasma HIV-1. V3 env aminoacidic sequences and net charge were consistent with M-R5 phenotype in all CSF and in most plasma clones. The degree of genetic heterogeneity (both complexity and diversity) in p17 gag was significantly lower in CSF-HIV than that in plasma-HIV for three patients, higher for one patient, and not significantly different for one patient, suggesting compartmentalization for all but the latter patient. When considering the pattern of CMP, the most abundant CMP observed in HIV from plasma and CSF was different in patients showing compartmentalization, while was the same in the patient without significant differences in CSF and plasma quasispecies. In conclusion, the present data on CMP pattern, V3 loop aminoacidic signature and genetic heterogeneity of HIV-1 quasispecies from CSF and plasma of HIVE patients, are consistent with a compartmentalized virus replication, at least in some patients, and with a possible different source of HIV in the two body sites, even though in a context of a largely prevalent M-R5 phenotype.

AIDS Dementia Complex↗
PubMed2004

Regulation of macrophage foam cell formation by alphaVbeta3 integrin: potential role in human atherosclerosis.

The accumulation of macrophage foam cells in atherosclerotic lesions is associated with both initiation and progression of this disease. Scavenger receptors CD36 and SRA are the primary receptors responsible for conversion of macrophages into foam cells. Integrin alphaVbeta3 plays a role in the differentiation of several cell types, but its involvement in the transition of macrophages into foam cells and the potential role of this receptor in atherosclerosis have not been examined. Using an in vitro model of single surface receptor activation by binding with an immobilized monoclonal antibody specific to alphaVbeta3 integrin we show that ligation of alphaVbeta3 integrin prevents differentiation of blood monocytes and macrophages into the foam cell phenotype via coordinate down-regulation of CD36 and SRA. This effect of alphaVbeta3 integrin ligation can be reproduced by contact with endothelial cells, whereas the inhibition of alphaVbeta3 receptor ligation restores the uptake of oxidized low-density lipoprotein. Moreover, we found that alphaVbeta3 integrin is readily detected in situ on macrophages in early and advanced atherosclerotic lesions and that in vitro exposure to oxidized low-density lipoprotein up-regulates alphaVbeta3 integrin expression. We hypothesize that alphaVbeta3 integrin regulates macrophage functional maturation into foam cells in a persistent manner, and therefore, by targeting alphaVbeta3 receptor it could potentially be possible to regulate progression of atherosclerosis in humans.

Adult↗