Peripheral blood mononuclear cells PBMCs

Since initial studies identified opioid receptors on T-lymphocytes (Wybran et al. 1979), the effects of opioids on immune function have been extensively studied. Details of these studies have been exhaustively reviewed (Madden et al. 1991 Adler et al. 1993 Peterson et al. 1998 Donahoe and Vlahov 1998 Roy et al. 2006), and will only be briefly mentioned here. In general, opioids suppress immune function. Peripheral leukocytes, including lymphocytes and peripheral blood mononuclear cells (PBMCs) can express the four major opioid receptor types, MOP, DOP, KOP,... 

Interferon-y (IFN-y) mRNA levels were measured in unstimulated peripheral blood mononuclear cell (PBMC) and purified cell populations, using a bDNA assay, to characterize the cell types that contribute to the in vivo increase in IFN-y gene expression seen in HIV infection (Breen et al 1997). IFN-y is a cytokine that can be produced by multiple cell types and is considered to enhance cellular responses by activation of monocytes and macrophages. It is one of the type 1 cy-... 

DPD Biochemical Phenotype Measured in Peripheral Blood Mononuclear Cells (PBMC)... 

Recently, it has been found that NO donors inhibit HIV-1 replication in acutely infected human peripheral blood mononuclear cells (PBMCs), and have an additive inhibitory effect on HIV-1 replication in combination with 3 -azido-3 -deoxythymisylate (AZT) [139, 140]. S-nitrosothiols (RSNOs) inhibit HIV-1 replication at a step in the viral replicative cycle after reverse transcription, but before or during viral protein expression through a cGMP-independent mechanism. In the latently infected U1 cell line, NO donors and intracellular NO production stimulate HIV-1 reactivation. These studies suggest that NO both inhibits HIV-1 replication in acutely infected cells and stimulates HIV-1 reactivation in chronically infected cells. Thus, NO donors may be useful in the treatment of HIV-1 disease by inhibiting acute infection, or reactivating a latent virus. 

For other efflux transporters such as BCRP (ABCG2), human pharmacokinetic and pharmacodynamic data are currently rare. However, an investigation of the influence of polymorphisms in ABC-transporter genes on the accumulation of nelfinavir in peripheral blood mononuclear cells (PBMCs) revealed no associations between the polymorphisms in the transporters analyzed and the accumulation of nelfinavir in the PBMCs [151], A second study in patients clearly demonstrated an increase in the AUC of the orally and intravenously administered BCRP substrate topotecan when it is given with GF120918, an inhibitor of P-glycoprotein and BCRP [152],... 

For primary isolation of HIV, patient peripheral blood mononuclear cells (PBMC) are collected, the usual inoculum being 106-107 cells. This is the most productive specimen, although virus has been cultured from plasma, semen, tears, saliva, breast milk, and brain tissue. The virus can be cultured from patient specimens at any time in the course of disease, during which the titer changes. Blood contains approximately 60 TCID50% (50% tissue culture infective dose) per milliliter when a person is asymptomatic, and about 7000TCID50/ml in later stages of HIV disease. 

Although cell lines are often used in preclinical studies, it is also important to test a compound on primary cells from the target tissue itself. Because this tissue must be taken from healthy, human volunteers, such tissue is often difficult to obtain in sufficient quantities for many types of assays that require large numbers of cells. In Figure 7.9, normal peripheral blood mononuclear cells (PBMCs) from four unrelated, healthy donors were treated... 

Normal peripheral blood mononuclear cells (PBMCs) from four unrelated, healthy donors treated with fludarabine all four of the control individuals had almost identical dose-response curves. 

To characterize IRIV-elicited immune responses in vitro, we addressed cell proliferation and cytokine expression in peripheral blood mononuclear cell (PBMC) cultures, as well as IRIV effects on dendritic cells (DC). In all experiments, PBMC were obtained from healthy donors and, if needed, further separated into different cell subsets. Finally, cells were cultured in the presence or absence of IRIV as indicated. 

Figure 2 Cytokine gene expression in immunopotentiating reconstituted influenza virosomes (IRIV) stimulated peripheral blood mononuclear cells (PBMC). PBMC were cultured in the presence or absence of IRIV. On days 1 and 2, culture cells were harvested and total cellular RNA was extracted and reverse transcribed. The cDNAs thus obtained were tested in real time polymerase chain reaction assays in the presence of primers specific for the indicated cytokine genes. Source From Refs. 6 and 9.

Figure 3 Cytokine secretion in immunopotentiating reconstituted influenza viro-somes (IRIV)-stimulated peripheral blood mononuclear cells (PBMC). PBMC from a healthy donor were cultured in the absence of stimuli (Neg) or in the presence of IRIV (V, 1 50 diluted) or control liposomes (L, 1 50 diluted). On days 1, 2, and 4 supernatants were harvested and the concentrations of interferon-y (A), GM-CSF (B), TNF-a (C), and interleukin-4 (D) were determined by ELISA. Abbreviations GM-CSF, granulocyte monocyte colony stimulating factor TNF-a, tumor necrosis factor-a. Source From Ref. 6.

Peripheral blood mononuclear cells (PBMCs) that include mainly monocytes, T-cells, and B-cells, and smaller portions of NK cells and dendritic cells of myeloid and plasmacytoid origin, are a critical component of immune system. PBMC-based models are widely used in research of cell-mediated immunity and for screening of compounds for immunomodulatory effects. 

Peripheral blood mononuclear cells (PBMC), cell number and differentiation... 

Fas transcripts are known to exist in normal cells in two differently spliced forms—the full-length or alternatively spliced variants encoding iriFas and sFas, respectively. Moreover at least seven variants of alternatively spliced Fas mRNA have been reported in peripheral blood mononuclear cells (PBMC) harvested from normal volunteers. Notably, these variants, encoding mainly sFas, are expressed... 

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