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PubMed1990

Decrease in interferon-gamma production by peripheral blood mononuclear cells in patients with uterine cervical cancer.

The interferon-gamma (IFN-gamma) productivity of peripheral blood mononuclear cells (PBMCs) was examined in 30 patients with uterine cervical cancer. The patients under 50 years of age had decreased IFN-gamma production compared with the age-matched controls. The IFN-gamma productivity in the patients over 50 years of age was decreased as well as in the age-matched controls. The proportion of monocytes in PBMCs did not correlate with the IFN-gamma productivity. The prostaglandin E2 (PGE2) productivity of PBMCs increased with the progress of cancer. PGE2 inhibited the IFN-gamma production by PBMCs, and the sensitivity of PBMCs to PGE2 was increased in the patients and controls over 60 years of age. The addition of indomethacin resulted in an increase in IFN-gamma production by PBMCs. These results suggest that the increased production of PGE2 and/or increased sensitivity to PGE2 are responsible for the decreased IFN-gamma production in patients with cervical cancer.

Adult↗
PubMed1997

Cytokine-mediated antitumor effect of OK-432 on urinary bladder tumor cells in vitro.

Fatal complications from the intravesical instillation of bacillus Calmette-Guérin (BCG) for the treatment of superficial urinary bladder tumors have been reported. OK-432, an immunomodulating agent like BCG, may be an effective and safe agent for the treatment of urinary bladder tumors. We investigated the cytokine-mediated antitumor effect of OK-432 on established human bladder cancer cell lines (T24 and KK-47) in vitro. Peripheral blood mononuclear cells (PBMCs) from a healthy volunteer were cultured with OK-432 for various periods, and the culture supernatants were used as conditioned media. Cytokines in the culture supernatants were quantified. The antitumor effect of OK-432 was evaluated by colony-forming assays, using the conditioned media as the culture media. The colony survival of T24 and KK-47 cells was significantly inhibited by conditioned media from 24-h cultures of PBMCs incubated with OK-432 at concentrations of 0.05 and 0.1 Klinische Einheit (KE)/ml. Conditioned media from PBMCs cultivated with OK-432 for 7 days at 0.01 and 0.05 KE/ml also significantly inhibited the colony survival of both cell lines. Higher concentrations of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) were detected in conditioned media cultivated with OK-432 for 24 h than in media from PBMCs alone. However, higher concentrations of interferon gamma (IFN gamma) were detected in conditioned media cultivated with OK-432 for 7 days. Approximately 90% of the inhibition of KK-47 cells by the 24-h conditioned media was neutralized by an anti-TNF monoclonal antibody. The inhibition of T24 cells was neutralized approximately 50% by the same antibody. The inhibition of T24 and KK-47 cells by 7-day conditioned media was completely neutralized by an anti-IFN gamma monoclonal antibody. The cultivation of PBMCs with OK-432 inhibited the production of granulocyte-colony-stimulating factor (G-CSF) by PBMCs. The inhibition may play a role in the mechanism of the antitumor effect of OK-432. Urinary bladder tumor cell lines have different sensitivities to cytokines. The cytokines induced by OK-432 vary with the concentration of OK-432 and the culture period. It is suggested that in intravesical instillation of OK-432 for treatment of urinary bladder tumor, the optimal dose and interval of instillation should be considered.

Antibodies, Monoclonal↗
PubMed2006

Telomerase activity in peripheral blood mononuclear cells from senile patients with pneumonia.

To investigate the changes of the activity of telomerase in peripheral blood mononuclear cells (PBMCs) from senile patients with pneumonia, the telomerase activity was examined before and after the stimulation of phytohemagglutinin-M (PHA-M) in PBMCs from 10 control subjects (group A), 12 non-senile patients with pneumonia (group B) and 9 senile patients with pneumonia (group C). Also observed was the proliferative response of these PBMCs to PHA-M. The results showed that, both with or without the stimulation of PHA-M, the values of telomerase activity in PBMCs from group C patients (A values: pre-stimulation, 0.43 +/- 0.04; post-stimulation, 0.63 +/- 0. 03) were significantly lower than those in PBMCs from both group A patients (A values: pre-stimulation, 0.65 +/- 0.05; post-stimulation, 1.26 +/- 0.13; P<0.001, respectively) and group B patients (A values: pre-stimulation, 0.63 +/- 0.03; post-stimulation, 0.93 +/- 0.03; P<0.05, respectively). The results of MTT test showed that the proliferative activity of PBMCs in group C patients (A value: 0.35 +/- 0.03) was also significantly lower than that in group A patients (A value: 0. 55 +/- 0.04; P<0.05) and group B patients (A value: 0.46 +/- 0.03; P<0.05). These results indicate that the telomerase activity decreases in senile patients with pneumonia, which may be one of the mechanisms for the weakened immune function in those patients.

Age Factors↗
PubMed1999

JTE-607, a novel inflammatory cytokine synthesis inhibitor without immunosuppression, protects from endotoxin shock in mice.

OBJECTIVE AND DESIGN: We investigated the effect of a novel N-benzoyl-L-phenylalanine derivative compound (JTE-607) on production of various cytokines and other immune responses in vitro and on endotoxin shock in vivo. MATERIALS AND METHODS: Human, monkey, rabbit, mouse and rat peripheral blood mononuclear cells (PBMCs), and human fibroblasts, umbilical vein endothelial cells (HUVEC), mesangial cells and T cells were used in vitro. Endotoxin shock was induced by lipopolysaccharide (LPS) in Corynebacterium parvum (C. parvum) sensitized male C57BL/6 mice in vivo. RESULTS: JTE-607 inhibited inflammatory cytokine production, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8 and IL-10, from LPS-stimulated human PBMCs, with IC50 values of 11, 5.9, 8.8, 7.3 and 9.1 nM, respectively. The inhibitory effects of JTE-607 were also seen in mRNA expression of those cytokines. The potency of JTE-607 on cytokine production from PBMCs of other species, and from other human cells were much lower than that on human PBMCs. JTE-607 did not affect either LPS-stimulated microbead phagocytosis or reactive oxygen species production at 1 microM in human PBMCs but slightly suppressed expression of major histocompatibility complex class II antigen at 1 microM, although it was 100-fold less active than it was as a cytokine inhibitor. JTE-607 (0.3-10 mg/kg, i.v.) showed dose dependent inhibition of mortality after LPS challenge in C. parvum sensitized mice in accordance with a decrease of plasma TNF-alpha. CONCLUSIONS: These results suggest that JTE-607 is a multiple cytokine inhibitor specific for human PBMCs. This compound may be useful for the treatment of various cytokine mediated diseases such as septic shock without causing immunosuppression.

Animals↗
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↗
PubMed2002

Ultrastructural localization of tyrosine hydroxylase in human peripheral blood mononuclear cells: effect of stimulation with phytohaemagglutinin.

Using immunocytochemistry coupled to fluorescence and electron microscopy, we investigated the expression and ultrastructural localization of tyrosine hydroxylase (TH, EC 1.14.16.2), the rate-limiting enzyme in the biosynthesis of catecholamines, in human peripheral blood mononuclear cells (PBMCs), with PC12 cells as positive controls. In unstimulated PBMCs, TH-specific immunoreactivity was localized to the plasma membrane. However, after stimulation with the polyclonal mitogen phytohaemagglutinin (PHA), TH immunoreactivity was almost completely localized to electron-dense cytoplasmic granules, which resembled those found in PC12. TH-positive granules, however, were larger (300-500 nm) than in PC12 cells (100-200 nm). Flow cytometry analysis of TH expression showed about 46-50% positive cells in unstimulated PBMCs and in PHA-stimulated PBMCs in the G0/G1 phase of the cell cycle, but more than 80% positive cells in PHA-stimulated PBMCs in the S+G2/M phase. In agreement with previous observations, PHA stimulation also induced de novo expression of TH mRNA as well as increased intracellular catecholamine content, suggesting the occurrence of TH upregulation at the level of both gene expression and enzyme activity. The ultrastructural localization of TH in human PBMCs seems therefore regulated by cell stimulation and related to the functional activity of the enzyme.

Humans↗
PubMed2005

Tumor necrosis factor-alpha up-regulation in spontaneously proliferating cells derived from bovine leukemia virus-infected cattle.

We previously reported that tumor necrosis factor alpha (TNF-alpha) was one of the cytokines that contributed to the leukemogenesis caused by bovine leukemia virus (BLV). To determine if the spontaneous cell proliferation observed in the late disease stages, such as persistent lymphocytosis and lymphosarcoma, correlated with the expression level of TNF-alpha, we analyzed the mRNA expression levels for TNF-alpha in spontaneously proliferating PBMCs derived from BLV-infected cattle. The mean mRNA expression level for TNF-alpha was higher in the spontaneously proliferating PBMCs derived from BLV-infected cattle than in non-spontaneously proliferating PBMCs from normal cattle. The TNF-alpha protein level in the PBMCs was determined by flow cytometric analysis, and it was noted that most of the cells expressing membrane-bound TNF-alpha in the spontaneously proliferating cells were CD5+ or sIgM+-cells. Additionally, in order to determine if this spontaneous proliferation can be blocked by anti-bovine TNF-alpha MAb, the spontaneously proliferating PBMCs from a BLV-infected cattle were cultured in the presence of the MAb. The addition of this MAb at the beginning of the 72 h-cultivation clearly inhibited spontaneous proliferation of cells in a dose-dependent manner, indicating the direct involvement of TNF-alpha in the spontaneous proliferation of PBMCs during the late disease stage. These data suggest that an aberrant expression of TNF-alpha might contribute to the progression of bovine leukosis in animals which develop persistent lymphocytosis of B-cells or B-cell lymphosarcoma.

Animals↗
PubMed1997

Determination of peripheral blood mononuclear cell responses to mitogens and woodchuck hepatitis virus core antigen in woodchucks by 5-bromo-2'-deoxyuridine or 2[3H]adenine incorporation.

Characterization of cellular immune response to antigens of woodchuck hepatitis virus (WHV) can contribute to the understanding of acute resolving and chronic outcome of hepadnavirus infection. Studies were limited because peripheral blood mononuclear cells (PBMCs) of woodchucks failed to incorporate [3H]thymidine sufficiently. Therefore, we established a non-radioactive proliferation assay for woodchuck PBMCs using 5-bromo-2'-deoxyuridine (BrdU) as thymidine analogue. Mitogen- and WHV core protein-(WHcAg) induced PBMC proliferation was detected by BrdU incorporation and compared to an assay using 2[3H]adenine. After stimulation with concanavalin A (ConA) and phytohaemagglutinin (PHA) we observed significant PBMC proliferation with both assays. Mitogen-induced nucleoside uptake of PBMCs into cellular DNA was confirmed by detection of 1',2'[3H]BrdU and 2[3H]adenine in extracted DNA. PBMCs obtained during the acute phase of WHV infection could be stimulated by WHcAg, whereas no WHcAg-induced proliferation of PBMCs was found in WHV-negative animals. PBMCs of chronic WHV carriers showed only a weak response to WHcAg. The established assays will be useful in determining the kinetics of cellular immune responses to different WHV antigens in the course of WHV infection and may provide an insight into mechanisms responsible for chronic outcome of hepadnavirus infection.

Adenine↗
PubMed2006

Evaluation of copper toxicity in isolated human peripheral blood mononuclear cells and it's attenuation by zinc: ex vivo.

Copper and zinc act as a cofactor of over 300 mammalian proteins. Both have same electronic configuration therefore they are antagonist at higher individual concentration. The present study was designed with the aim to investigate the mechanisms pertaining to toxic effects of copper on human peripheral blood mononuclear cells (PBMCs) and to evaluate the cytoprotective effect of zinc on copper-induced cytotoxicity. The copper uptake into PBMCs was progressively increased with increasing concentration of metal in the growth medium. However, no significant effect on copper uptake was observed in the presence of zinc. Cell proliferation rate was decreased with increasing copper concentration. Interestingly, the proliferation rate of zinc treated PBMCs remained nearly the same as that of control cells. LD(50) of copper (115 microM) was increased six times (710 microM) in presence of zinc for PBMCs. At higher concentrations of copper (> 100 microM) decrease level of GSH was noticed. Increased levels of metallothionein in PBMCs were observed in response to zinc. DNA fragmentation studies also showed that copper produced DNA fragmentation at LD(50) (115 microM). Subsequently, zinc showed protection against DNA fragmentation caused by copper. Cell structure of PBMCs at LD(50) (115 microM copper) showed membrane bound cystic spaces and mitochondria having disrupted cristae and few myelin figures. In presence of zinc at LD(50) of copper (115 microM) cells showed improvement in mitochondrial structure and membrane bound cystic spaces. Taken together, the results of our study demonstrates that zinc play an important role in prevention of copper toxicity in peripheral blood mononuclear cells.

Cell Membrane↗
PubMed1993

Pokeweed mitogen induces IgE synthesis in the presence of a blocking antibody to the interferon-gamma receptor.

BACKGROUND: Although pokeweed mitogen (PWEM) can induce peripheral blood mononuclear cells (PBMCs) to synthesize IgG, IgA, and IgM, such cultures fail to induce IgE synthesis. The present study examined the possibility that the stimulation of interferon-gamma (IFN-gamma) production plays a role in the failure of PWM to induce IgE synthesis. METHODS: We examined PBMCs from eight normal control subjects for IFN-gamma and IL-4 production. Since IFN-gamma synthesis is known to inhibit IgE synthesis, we also examined the effect of a neutralizing anti-IFN-gamma antibody and of two anti-IFN-gamma receptor antibodies, monoclonal antibody (mAb) GIR208, which blocks cellular binding of IFN-gamma, and mAB GIR94.5, which binds to the IFN-gamma receptor but does not block the binding of IFN-gamma to its receptor on PWM-stimulated PBMCs. RESULTS: After stimulation with PWM, culture supernatants contained significantly more IFN-gamma (p = 0.001) and IL-4 (P = 0.001) compared with supernatants from nonstimulated cultures. PWM-stimulated PBMCs also expressed higher levels of IFN-gamma and IL-4 gene transcripts than unstimulated cells. When cultured in the presence of anti-IFN-gamma, supernatants from PWM-stimulated cultures also induced CD23 on Ramos B cells in an IL-4-dependent manner. In the presence of mAB GIR208 and a neutralizing anti-IFN-gamma antibody, but not mAb GIR94.5, PWM stimulated PBMCs from eight normal control subjects and six patients with atopic dermatitis to produce IgE. Monoclonal antibody GIR208, however, did not enhance IgG synthesis. Furthermore, the exogenous addition of IFN-gamma inhibited the IgE-stimulatory effect of mAb GIR208. Monoclonal antibody GIR208 was unable to induce purified B cells to synthesize IgE in the presence of IL-4. CONCLUSIONS: Thus unlike anti-CD40, mAb GIR208 does not act as a second signal for the induction of IgE synthesis. These results demonstrate that the induction of IFN-gamma production contributes to the failure of PWM to stimulate synthesis of IgE in PBMCs from atopic and nonatopic donors.

Adult↗
PubMed1993

Lol p I-induced IL-4 and IFN-gamma production by peripheral blood mononuclear cells of atopic and nonatopic subjects during and out of the pollen season.

The reciprocal effects of IL-4 and IFN-gamma on IgE synthesis have been well established. It has also been shown that these two lymphokines are secreted by different subsets of CD4+ T cells (TH1 and TH2), and that TH2 helper T lymphocytes could be involved in the pathophysiology of allergic diseases. But little is known about the effects of an allergen on the profile of lymphokine synthesis by human peripheral blood mononuclear cells (PBMCs) of allergic and nonallergic subjects. We studied the production of IL-4 and IFN-gamma by PBMCs of atopic and nonatopic donors after in vitro stimulation by the group 1 allergen from Lolium perenne pollen (Lol p I), during and out of the grass pollen season. On natural exposure to pollen, Lol p I-induced IL-4 production was observed only with atopic donors (6 of 8), whereas the synthesis of IFN-gamma was observed for all nonatopic donors (7 of 7) and most allergic patients (5 of 7). At the time of the study, higher amounts of IFN-gamma were produced by PBMCs of nonatopic donors than by PBMCs of atopic patients. Out of the pollen season the production of IL-4 was not observed either by atopic (n = 11) or by nonatopic subjects (n = 5). On the other hand, IFN-gamma was produced by PBMCs of most subjects (atopic, 10 of 11; nonatopic, 5 of 5), but at the time of the study no difference was observed between the two groups. These results show that Lol p I induces different profiles of IL-4 and IFN-gamma production by PBMCs of atopic and nonatopic subjects. In atopic subjects this profile of lymphokine synthesis is influenced by the natural exposure to pollen, which is in keeping with the seasonal rise of IgE antibodies.

Adult↗
PubMed1994

The production of interferon-gamma in response to a major peanut allergy, Ara h II correlates with serum levels of IgE anti-Ara h II.

The current study was undertaken to examine the potential role of T cells in the pathogenesis of peanut allergy. Peripheral blood mononuclear cells (PBMCs) from patients with peanut allergy, patients with asthma, and nonatopic normal control subjects were assessed for proliferation after stimulation with a 17 kd major peanut allergen (Ara h II), ovalbumin, casein, soy, and Candida albicans. We found that Ara h II and C. albicans induced significantly higher levels of proliferation than ovalbumin, casein, and soy. Because interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) play critical roles in IgE regulation, we assessed the production of these cytokines after stimulation with C. albicans and Ara h II. C. albicans stimulated similar levels of IFN-gamma in all three study groups. In contrast, after stimulation with Ara h II, culture supernatants from PBMCs of subjects with peanut allergy contained significantly lower levels of IFN-gamma than did the PBMCs of the two control groups (p = 0.02). More important, there was a significant (p = 0.05) inverse correlation between the serum IgE anti-Ara h II levels and IFN-gamma production by PBMCs from the respective peanut-allergic patients. IL-4 protein was not detected in culture supernatants of PBMCs stimulated with Ara h II. However, amplification of cytokine gene transcripts by polymerase chain reaction did demonstrate IL-4 expression in Ara h II-stimulated PBMCs from both patients with peanut allergy and control subjects. These data suggest that the level of IFN-gamma production in response to Ara h II may be an important factor in determining the development of peanut-specific IgE responses.

2S Albumins, Plant↗
PubMed2004

Interleukin-6 (IL-6) expression and natural killer (NK) cell dysfunction and anergy in heart failure.

Immune dysfunction has been postulated to play a role in the pathophysiology of chronic heart failure. We examined the relation between interleukin-6 (IL-6) production and natural killer (NK) cell dysfunction in patients with chronic heart failure. Sera and peripheral blood mononuclear cells (PBMCs) were collected from 82 patients with advanced heart failure. Levels of circulating NK cells and T cells were determined by flow cytometry. NK cell function was measured by standard cytotoxicity assays. IL-6 in supernatants of PBMC cultured in vitro was quantitated by an enzyme-linked immunosorbent assay. The levels of circulating NK cells were lower in patients with heart failure than in normal controls (p = 0.0037). NK cells from patients with heart failure also exhibited impaired cytolytic functions in the absence of stimuli and in response to IL-2 and IL-12 (p <0.0001 for all conditions). PBMCs from patients with heart failure produced higher levels of IL-6 in response to a T-cell stimulus than did PBMCs from healthy controls (p = 0.0012). The level of IL-6 produced by unstimulated PBMCs in patients with heart failure correlated with NK cell cytolytic impairment (p = 0.0012). These results demonstrated that PBMCs are a source of IL-6 in patients with heart failure. Production of IL-6 by PBMCs correlated with NK cell anergy to other cytokines that use signal transduction pathways that may be regulated by IL-6. These results support a model of cytokine-induced anergy in conditions that result in high systemic levels of IL-6.

Adult↗
PubMed2005

Sex differences in cytokine production and surface antigen expression of peripheral blood mononuclear cells after surgery.

BACKGROUND: Several clinical and epidemiological studies have observed a better outcome after sepsis in women than in men. The purpose of this study was to determine if these sex differences are observed in cytokine responses and the surface antigen expression of monocytes. In addition, the clinical courses of male and female patients after gastrointestinal surgery were compared. METHODS: A total of 25 patients with gastric carcinoma who underwent gastrectomy were enrolled in this study. Tumor necrosis factor-alpha (TNF-alpha), interleukin-10, and interferon-gamma (IFN-gamma) production by lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMCs) as well as the expression of Toll-like receptor-4 (TLR-4), TLR-2, human leukocyte antigen-D related (HLA-DR), and CD16 on monocytes in 16 men and 9 women on the day before surgery were compared with measurements on postoperative day (POD) 1. Furthermore, postoperative infectious complications, the development of systemic inflammatory response syndrome, and serum C-reactive protein levels on POD3 were compared. RESULTS: TNF-alpha production of PBMCs and TLR-2 and CD16 expression on monocytes were significantly higher in women than in men before surgery. IFN-gamma production of PBMCs and HLA-DR expression on monocytes were significantly lower in men than in women on POD1. Furthermore, TNF-alpha production of PBMCs on POD1 was significantly increased, and both IFN-gamma production and HLA-DR expression were significantly decreased compared with that observed before surgery in men, but no corresponding significant changes were observed in women. In addition, C-reactive protein levels on POD3 were significantly higher in men than in women. CONCLUSIONS: Both TNF-alpha and interleukin-10 production of PBMCs and both TLR-2 and CD16 expression on monocytes were significantly higher in women than in men on the day before surgery. Excessive TNF-alpha and suppressive IFN-gamma production of PBMCs, as well as a decrease in HLA-DR expression on monocytes, occurred more often in men than in women after surgery, suggesting that these factors all contribute to an increased susceptibility of men to develop systemic inflammatory response syndrome or postoperative infectious complications.

Adult↗
PubMed2005

Expression of the drug transporters MDR1/ABCB1, MRP1/ABCC1, MRP2/ABCC2, BCRP/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver.

ATP binding cassette (ABC)-transporters like P-glycoprotein (multidrug resistance (MDR)1/ABCB1), the multidrug resistance associated proteins 1 and 2 (MRP1/ABCC1 and MRP2/ABCC2), and the breast cancer resistance protein (BCRP/ABCG2) have a large impact on the pharmacokinetics of numerous drugs and may also modulate the effectiveness of drug therapy. Prediction of a patient's susceptibility to xenobiotics and individualization of drug therapy would become possible, if a simple test were available for an easy screening of transporter expression. This study quantified the mRNA expression of the four ABC-transporters and of the pregnane X receptor (PXR), a key regulator in drug metabolism and efflux, in peripheral blood mononuclear cells (PBMCs), and corresponding liver or small intestine samples of humans by real-time reverse transcription-polymerase chain reaction (RT-PCR). The results obtained prove the absence of a correlation between the expression of four major ABC-transporters in PBMCs and in the intestine or liver. For all transporters (except MRP1/ABCC1 in the intestine), mRNA amount of the ABC-transporters was positively correlated with PXR expression in PBMCs and intestine. In conclusion, the study suggests that basal expression levels of the transporters are directly influenced by PXR expression in liver and PBMCs and demonstrates that PBMCs do not qualify as surrogate tissue for the expression of the four ABC-transporters in small intestine and liver. However, the transporter status in PBMCs remains important for drugs, whose primary site of therapeutic action is the lymphocyte and which are known substrates of the transporters.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2004

Increased caspase activation in peripheral blood mononuclear cells of patients with Alzheimer's disease.

In this study, we investigated whether alterations in the pattern of caspase activation could be found at the level of peripheral blood mononuclear cells (PBMCs) in patients with Alzheimer's disease (AD). The results showed that in experimental conditions resembling a physiological stimulation, there was a statistically significant increase in the enzymatic activity of caspase-3, caspase-8, and caspase-9 in PBMCs from a small, but well-characterized, cohort of sporadic AD patients compared to those from a comparable control group of aged adults (AA). This was accompanied by a parallel, early increase in the cleavage activity of the same caspases. The higher level of caspase activity in PBMCs from AD compared to AA was not associated with quantitative differences in cell subset profiles. Moreover, no increase in apoptosis level, in the same experimental conditions, was found in PBMCs from this cohort of AD patients compared to those from AA. Conversely, the higher proneness to caspase activation in PBMCs from AD patients in comparison with that from AA was associated with a higher proliferative response to PHA or CD3. These data show a new dysfunction in AD patients at the PBMCs level and suggest that increased proneness to caspase activation in lymphocytes could reflect an ongoing systemic response in neurodegenerative disease with pathogenetic implications.

Adult↗
PubMed2005

Increased cyclooxygenase-2 expression in peripheral blood mononuclear cells of smokers and hyperlipidemic subjects.

Cyclooxygenase (COX)-2 is expressed in macrophages of arteriosclerotic lesions and promotes inflammation. We investigated whether COX-2 is already expressed in peripheral blood mononuclear cells (PBMCs) of subjects possessing risk-related factors, such as in smokers and hyperlipidemics. PBMCs were isolated from the venous blood of normolipidemic nonsmokers (NL-NSM; n = 15), normolipidemic smokers (NL-SM; n = 12), hyperlipidemic nonsmokers (HL-NSM; n = 10), and hyperlipidemic smokers (HL-SM; n = 10). RNA from PBMCs was used for RT-PCR. Plasma concentrations of oxidized low-density lipoproteins (oxLDL) were measured by ELISA, those of glutamate and cystine by HPLC. The results show that COX-2 expression in PBMCs was significantly increased in the groups with cardiovascular risk factors (NL-SM, HL-SM, HL-NSM) compared with NL-NSM. COX-2 expression in PBMCs was positively correlated with concentrations of total serum cholesterol, oxLDL, glutamate, or cystine. We suggest that the elevated COX-2 expression indicates a priming of PBMCs as a response to a systemic pro-oxidative and proinflammatory shift in subjects with cardiovascular risk factors, which might also contribute to growth and instability of arteriosclerotic lesions.

Adult↗
PubMed2006

Expression of mRNA for multiple serotonin (5-HT) receptor types/subtypes by the peripheral blood mononuclear cells of rhesus macaques.

To find out whether rhesus macaque peripheral blood mononuclear cells (PBMCs) express mRNA for 5-HT receptors, blood samples from normal healthy rhesus monkeys were used to isolate PBMCs by Ficoll-paque density gradient centrifugation. Total RNA was extracted from MT-2 cells, Hut-78 cells, naive or phytohemagglutinin (PHA) stimulated human and monkey PBMCs. One tube RT-PCR was performed using primers specific for human 5-HT1A, 5-HT1B, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors. Amplicons of expected sizes were obtained from human cell lines as well as both human and monkey PBMCs. Both PHA stimulated human and monkey PBMCs express mRNAs for 5-HT1A, 5-HT1B, 5-HT1E, 5-HT2A, 5-HT3, 5-HT4, 5-HT6 receptor types/subtypes. However, mRNAs for 5-HT1B, 5-HT1E and 5-HT2A cannot be confidently detected in some of the PBMC samples without PHA stimulation. 5-HT2B and 5-HT7 receptor mRNA was not detected in most of the samples and 5-HT2C receptor mNRA was not detected at all. FACS analysis revealed that CD3+ lymphocyte increased more than 20% among lymphocytes in the PHA stimulated PBMCs. These data indicate that similar to human PBMC, rhesus macaque PBMC may express multiple types of 5-HT receptors and the expression profile could change after PHA stimulation due to either the changes in cell composition or changes in gene transcription level. This provided a basis for further studies on the neuroimmunomodulatory interactions of 5-HT in rhesus macaques.

Animals↗