UMLS:C0021051 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of urokinase-type plasminogen activator (uPA) to its glycosyl-phosphatidyl-inositol (GPI) anchored receptor (uPAR) mediates a variety of functions in terms of vascular homeostasis, inflammation and tissue repair. Both uPA and uPAR, as well as their soluble forms detectable in plasma and other body fluids, represent markers of cancer development and metastasis, and they have been recently described as predictors of human immunodeficiency virus (HIV) disease progression, independent of CD4+ T cell counts and viremia. A direct link between the uPA/uPAR system and HIV infection was earlier proposed in terms of cleavage of gp120 envelope by uPA. More recently, a negative regulatory effect on both acutely and chronically infected cells has been linked to the noncatalytic portion of uPA, also referred to as the amino-terminal fragment (ATF). ATF has also been described as a major CD8+ T cell soluble HIV suppressor factor. In chronically infected promonocytic U1 cells this inhibitory effect is exerted at the very late stages of the virus life cycle, involving virion budding and entrapment in intracytoplasmic vacuoles, whereas its mechanism of action in acutely infected cells remains to be defined. Since uPAR is a GPI-anchored receptor it requires association with a signaling-transducing component and different partners, which include CD11b/CD18 integrin and a G-protein coupled receptor homologous to that for the bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalanine. Which signaling coreceptor(s) is(are) responsible for uPA-dependent anti-HIV effect remains currently undefined.
...
PMID:The role of urokinase-type plasminogen activator (uPA)/uPA receptor in HIV-1 infection. 1296 Feb 38

CD4C/human immunodeficiency virus (HIV) transgenic mice develop an AIDS-like disease. We used this model to study the effects of HIV-1 on dendritic cells (DC). We found a progressive decrease in total DC numbers in the lymph nodes, with a significant accumulation of CD11b(Hi) DC. In the thymus, the recovery of transgenic CD8alpha(+) DC had a tendency to be lower. Spleen DC were augmented in the marginal zone. Transgenic DC showed a decreased capacity to present antigen in vitro, consistent with their reduced major histocompatibility complex class II expression and impaired maturation profile. The accumulation of immature DC may contribute to disease and may reflect an adaptive advantage for the virus by favoring its replication and preventing the generation of fully functional antiviral responses.
...
PMID:The AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with accumulation of immature CD11bHi dendritic cells. 1455 58

Increased central nervous system (CNS) levels of monocyte chemoattractant protein 1 [CC chemokine ligand 2 (CCL2) in the systematic nomenclature] have been reported in chronic neurological diseases such as human immunodeficiency virus type 1-associated dementia, amyotrophic lateral sclerosis, and multiple sclerosis. However, a pathogenic role for CCL2 has not been confirmed, and there is no established model for the effects of chronic CCL2 expression on resident and recruited CNS cells. We report that aged (>6 months) transgenic (tg) mice expressing CCL2 under the control of the human glial fibrillary acidic protein promoter (huGFAP-CCL2hi tg+ mice) manifested encephalopathy with mild perivascular leukocyte infiltration, impaired blood brain barrier function, and increased CD45-immunoreactive microglia, which had morphologic features of activation. huGFAP-CCL2hi tg+ mice lacking CC chemokine receptor 2 (CCR2) were normal, showing that chemokine action via CCR2 was required. Studies of cortical slice preparations using video confocal microscopy showed that microglia in the CNS of huGFAP-CCL2hi tg+ mice were defective in expressing amoeboid morphology. Treatment with mutant CCL2 peptides, a receptor antagonist and an obligate monomer, also suppressed morphological transformation in this assay, indicating a critical role for CCL2 in microglial activation and suggesting that chronic CCL2 exposure desensitized CCR2 on microglia, which in the CNS of huGFAP-CCL2hi tg+ mice, did not up-regulate cell-surface expression of major histocompatibility complex class II, CD11b, CD11c, or CD40, in contrast to recruited perivascular macrophages that expressed enhanced levels of these markers. These results indicate that huGFAP-CCL2hi tg+ mice provide a useful model to study how chronic CNS expression of CCL2 alters microglial function and CNS physiology.
...
PMID:Chronic expression of monocyte chemoattractant protein-1 in the central nervous system causes delayed encephalopathy and impaired microglial function in mice. 1585 90

To gain insight into the role of dendritic cells (DCs) in feline immunodeficiency virus (FIV) infection and immunity, methods were developed to culture feline myeloid DCs from CD14(+) monocytes with a combination of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) and interleukin-4 (hrIL-4). These cells were compared with feline macrophages cultured in the presence of hrGM-CSF. As with DCs in other species, feline DCs showed uniformly high MHC class II expression, moderate B7.1 expression, potent induction of the allogeneic mixed leucocyte reaction (MLR), and moderate uptake of fluorescein isothiocyanate-dextran (FITC-DX) in the endocytic assay. In comparison with feline macrophages, DCs showed higher expression of MHC class II, similar expression of B7.1, CD14, CXCR4 and CD1a, and lower expression of CD11b. When placed on alcian blue-coated glass slides, DCs differed from macrophages in showing a greater tendency to spread out; they also had characteristic fine cytoplasmic processes instead of the broader pseudopodia of macrophages. Basal IL-12 mRNA expression and FITC-DX uptake were greater in DCs than in macrophages. Unlike feline DCs, feline macrophages exhibited a dose-dependent suppressive effect in the MLR. Feline DCs propagated in vitro should prove useful in the development of DC-mediated vaccination and therapy for infectious and neoplastic feline diseases. Additionally, macrophages cultured with GM-CSF provide a potential means of studying the mechanism of immunosuppression in cats.
...
PMID:Culture and comparison of feline myeloid dendritic cells vs macrophages. 1603 26

Increased expression of CD11b, the beta-integrin marker of microglia, represents microglial activation during neurodegenerative inflammation. However, the molecular mechanism behind increased microglial CD11b expression is poorly understood. The present study was undertaken to explore the role of nitric oxide (NO) in the expression of CD11b in microglial cells. Bacterial lipopolysaccharide (LPS) induced the production of NO and increased the expression of CD11b in mouse BV-2 microglial cells and primary microglia. Either a scavenger of NO (PTIO) or an inhibitor of inducible nitric-oxide synthase (L-NIL) blocked this increase in microglial CD11b expression. Furthermore, co-microinjection of PTIO with LPS was also able to suppress LPS-mediated expression of CD11b and loss of dopaminergic neuronal fibers and neurotransmitters in striatum in vivo. Similarly, other inducers of NO production such as interferon-gamma, interleukin-1beta, human immunodeficiency virus type-1 gp120, and double-stranded RNA (poly(IC)) also increased the expression of CD11b in microglia through NO. The role of NO in the expression of CD11b was corroborated further by the expression of microglial CD11b by GSNO, an NO donor. Because NO transduces many intracellular signals via guanylate cyclase (GC), we investigated the role of GC, cyclic GMP (cGMP), and cGMP-activated protein kinase (PKG) in microglial expression of CD11b. Inhibition of LPS- and GSNO-mediated up-regulation of CD11b either by NS2028 (a specific inhibitor of GC) or by KT5823 and Rp-8-bromo-cGMP (specific inhibitors of PKG), and increase in CD11b expression either by 8-bromo-cGMP or by MY-5445 (a specific inhibitor of cGMP phosphodiesterase) alone suggest that NO increases microglial expression of CD11b via GC-cGMP-PKG. In addition, GSNO induced the activation of cAMP response element-binding protein (CREB) via PKG that was involved in the up-regulation of CD11b. This study illustrates a novel biological role of NO in regulating the expression of CD11b in microglia through GC-cGMP-PKG-CREB pathway that may participate in the pathogenesis of devastating neurodegenerative disorders.
...
PMID:Up-regulation of microglial CD11b expression by nitric oxide. 1655 37

Recently we reported that monocyte phagocytosis and chemotaxis are impaired in X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVI) patients. Few data exist on the in vivo expression of receptors for the constant region of immunoglobulin (IgG) (Fc gammaR) and complement receptors (CR) in these patients. The objective of this study was to investigate the expression of Fc gammaR and CR on monocytes from XLA and CVI patients and compare it to that of healthy controls. Whole blood samples were obtained from 10 patients with XLA, 12 with CVI and 18 healthy controls. Monocyte phenotype was determined by flow cytometry with gating on CD14+ cells. Surface expression of Fc gammaRI (CD64), Fc gammaRII (CD32) and Fc gammaRIII (CD16), CR1 (CD35) and CR3 (CD11b and CD18) was measured by determination of the proportion of CD14+ cells positive for each receptor and by receptor density. Compared to controls, a significantly higher percentage of CD16 and CD35+ monocytes from XLA (P = 0.002 and P = 0.007, respectively) were observed. The relative fluorescence intensity (RFI) expression of Fc gammaRII (CD32) and Fc gammaRIII (CD16) were significantly lower on CVI monocytes compared to controls (P = 0.001 and P = 0.035, respectively). XLA patients, who have a reduction of Bruton's tyrosine kinase (Btk), showed normal or increased percentages of monocytes expressing Fc gamma and complement receptors. CVI patients, who have normal expression of Btk, showed reduced expression of CD16 and CD32 on monocytes. Inefficient chemotaxis and phagocytosis, reported previously in XLA patients, could be due to defects of cytoplasmatic transduction mechanisms.
...
PMID:Expression of Fc gamma and complement receptors in monocytes of X-linked agammaglobulinaemia and common variable immunodeficiency patients. 1790 Mar

Pathology due to the immune system's response to viral infections often represents a delicate balance between inhibition of viral pathogenesis and regulation of protective immunity. In susceptible C57BL/6 (B6) mice, the murine retroviral isolate LP-BM5 induces splenomegaly, hypergammaglobulinemia, profound B- and T-cell immunodeficiency, and increased susceptibility to opportunistic pathogens and terminal B-cell lymphomas. Here, we report that B6.PD-1 (programmed death-1) and B6.IL-10 knockout mice are substantially more susceptible to LP-BM5-induced disease than wild-type B6 mice. LP-BM5-infected B6.PD-1(-/-) mice developed more severe splenomegaly, hypergammaglobulinemia, and immunodeficiency than infected B6 mice: PD-1(-/-) mice are more susceptible to lower doses of LP-BM5 and show more exaggerated disease early postinfection. LP-BM5-infected B6.IL-10(-/-) mice also develop exaggerated LP-BM5-induced disease, compared to B6 mice, without a significant change in the retroviral load. By reciprocal reconstitution experiments, comparing wild-type versus PD-1(-/-) sources of the requisite cells for LP-BM5 pathogenesis-CD4 T and B cells, PD-1(+) B cells appear to be crucial in the normal limitation of LP-BM5-induced disease in B6 mice. Also, infected B6 mice have increased CD11b(+) spleen cells that express interleukin-10 (IL-10). However, PD-1(-/-) mice, though showing an even greater expansion of CD11b(+) cells after LP-BM5 inoculation, did not show an equivalent increase in IL-10-producing cells. Thus, it appears that PD-1/PD-L interactions and IL-10 are primarily important in moderating the effects of LP-BM5-induced disease in B6 mice.
...
PMID:The programmed death-1 and interleukin-10 pathways play a down-modulatory role in LP-BM5 retrovirus-induced murine immunodeficiency syndrome. 1809 75

There is increasing evidence that opiates accelerate the pathogenesis and progression of acquired immunodeficiency syndrome (AIDS), as well as the incidence of human immunodeficiency virus (HIV) encephalitis (HIVE), a condition characterized by inflammation, leukocyte infiltration, and microglial activation. The mechanisms, by which the HIV-1 transactivating protein Tat and opioids exacerbate microglial activation, however, are not fully understood. In the current study, we explored the effects of morphine and HIV-1 Tat(1-72) on the activation of mouse BV-2 microglial cells and primary mouse microglia. Both morphine and Tat exposure caused up-regulation of the chemokine receptor CCR5, an effect blocked by the opioid receptor antagonist naltrexone. Morphine in combination with Tat also induced morphological changes in the BV-2 microglia from a quiescent to an activated morphology, with a dramatic increase in the expression of the microglial activation marker CD11b, as compared with cells exposed to either agent alone. In addition, the mRNA expression of inducible nitric oxide synthase (iNOS), CD40 ligand, Interferon-gamma-inducible protein 10 (IP-10), and the proinflammatory cytokines tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6, which were elevated with Tat alone, were dramatically enhanced with Tat in the presence of morphine. In summary, these findings shed light on the cooperative effects of morphine and HIV-1 Tat on both microglial activation and HIV coreceptor up-regulation, effects that could result in exacerbated neuropathogenesis.
...
PMID:Morphine enhances Tat-induced activation in murine microglia. 1946 31

Thymic function decreases in line with tumor progression in patients with cancer, resulting in immunodeficiency and a poor prognosis. In the present study, we attempted to restore thymic function by BALB/c (H-2(d)) syngeneic (Syn), or B6 (H-2(b)) allogeneic (Allo) bone marrow transplantation (BMT) using intra-bone marrow-bone marrow transplantation (IBM-BMT) plus Syn-, Allo- or C3H (H-2(k)) 3rd-party fetal thymus transplantation (TT). Although the BALB/c mice with advanced tumors (Meth-A sarcoma; H-2(d), >4 cm(2)) treated with either Syn- or Allo-BMT alone showed a slight improvement in survival compared with non-treated controls, the mice treated with BMT + TT showed a longer survival. The mice treated with Allo-BMT + Allo-TT or 3rd-party TT showed the longest survival. Interestingly, although there was no difference in main tumor size among the BMT groups, lung metastasis was significantly inhibited by Allo-BMT + Allo-TT or 3rd-party TT. Numbers of CD4(+) and CD8(+) T cells, Con A response, and IFN-gamma production increased significantly, whereas number of Gr-1(+)/CD11b(+) myeloid suppressor cells and the percentage of FoxP3(+) cells in CD4(+) T cells significantly decreased in these mice. Furthermore, there was a positive correlation between survival days and the number of T cells or T cell function, while there was a negative correlation between survival days and lung metastasis, the number of Gr-1(+)/CD11b(+) cells, or the percentage of FoxP3(+) cells. These results suggest that BMT + TT, particularly Allo-BMT + Allo-TT or 3rd-party TT, is most effective in prolonging survival as a result of the restoration of T cell function in hosts with advanced tumors.
...
PMID:Prolonged survival in mice with advanced tumors treated with syngeneic or allogeneic intra-bone marrow-bone marrow transplantation plus fetal thymus transplantation. 2022 83

Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. A 13-year-old girl diagnosed LAD-I at the age of 7 years was brought to the Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, because of a draining plaque on the left leg for 2.5 years. She had recurrent skin infections and had been treated with repeated courses of different antibiotic combinations, with temporary responses, since 5 years of age. Examination revealed a 7 x 8 cm minimally erythematous hyperpigmented plaque with multiple draining sinuses on the left leg. Tissue culture yielded Pseudomonas aeruginosa. Flow cytometry showed CD18 (18.79%), CD11a (51.59%), CD11b (18.61%) and CD11c(10.60%). A plain radiography of the left leg revealed osteomyelitis. It is highly suggested that patients diagnosed mild to moderate LAD-1 with recurrent skin infection and simultaneous weak response to conventional therapy undergo (BMT) marrow transplant to prohibit subsequent life-threatening complications.
...
PMID:Osteomyelitis in leukocyte adhesion deficiency type 1 syndrome. 2035 60

<< Previous 1 2 3 4 5 6 7 Next >>