Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal macrophages in MRL-lpr mice are implicated in the pathogenesis of autoimmune disease. These mice die of lupus nephritis by 5 to 6 months of age. This study reports that MRL-lpr mice have an increased level of circulating macrophage colony-stimulating factor (M-CSF) detectable as early as 1 week of age. Macrophage colony-stimulating factor decreased between 2 and 4 months and then steadily increased beginning at 4 months of age. In contrast, M-CSF was not detected in sera from congenic MRL-++ mice, normal C3H/FeJ mice, two other mouse strains with the lpr gene (B6-lpr and C3H-lpr), or another lupus model, the NZB/W mouse. These observations indicate that the lpr gene alone is not responsible for inducing this growth factor, and elevated M-CSF is not required for all forms of murine lupus. The entire source of serum M-CSF is not clear. The unique T cells regulated by the lpr gene are not responsible for the increased serum M-CSF levels, as no M-CSFs could be detected in supernatants from cultured lymph nodes from MRL-lpr mice, and the steady-state levels of M-CSF mRNA in lymph nodes and spleens in MRL-lpr, C3H-lpr mice and in their respective congenic strains were similar. The steady-state M-CSF mRNA transcripts in liver, lung, and bone marrow in MRL-lpr, MRL-++, and C3H/FeJ mice were also similar. Macrophage colony-stimulating factor transcripts were clearly elevated in the kidneys of MRL-lpr mice, suggesting a renal source of circulating M-CSF. The increase of M-CSF might be responsible for the increased numbers and enhanced functions of macrophages, which in turn cause tissue destruction in MRL-lpr mice.
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PMID:Increased macrophage colony-stimulating factor in neonatal and adult autoimmune MRL-lpr mice. 186 17

Systemic lupus erythematosus is an autoimmune disease, characterized by high titers of autoantibodies against many cell-membrane and intracellular antigens. Polyclonal B cell activation and alterations in the T cell compartment have been described. The present report deals with the organ-associated macrophage (M phi) system of two lupus-prone mouse strains (NZB/W and MRL lpr/lpr) and demonstrates that in both mouse strains the M phi compartment of liver and spleen is clearly expanded. In the liver the number of F 4/80+ M phi is strongly elevated. In addition, presence of early M phi precursors and of extramedullary organ-associated monocyte proliferation in response to colony-stimulating factor (CSF) is documented in liver and spleen of these mice. Further, in normal animals during the first two weeks of life extramedullar monocytopoiesis is present in liver and spleen, which is then down-regulated in the third week of life. In the two lupus-prone mouse strains down-regulation does not occur but extramedullar monocyte proliferation is sustained at high level throughout life time. As possible correlates for the expansion of the M phi system elevated CSF-1 mRNA levels are demonstrated in kidney, spleen and liver of NZB/W mice and elevated CSF serum levels are documented in MRL lpr/lpr mice. The possible contribution of the expanded M phi system to B and T cell dysregulation is discussed.
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PMID:Expansion and high proliferative potential of the macrophage system throughout life time of lupus-prone NZB/W and MRL lpr/lpr mice. Lack of down-regulation of extramedullar macrophage proliferation in the postnatal period. 188 63

Autoimmune-thrombocytopenia was the striking feature in a patient with typical clinical symptoms of systemic lupus erythematosus (SLE), complement C4 deficiency, and positive lupus serology. However, myelodysplasia was found in the bone marrow and chromosome analysis revealed a deletion of the long arm of chromosome 5 (5q-anomaly), which was confirmed by a hemizygosity for the c-fms oncogene (CSF-1-receptor) on Southern blot. Autoimmune phenomena reported in conjunction with myelodysplastic syndromes (MDS), e.g., an elevation of antinuclear antibodies, are usually regarded as nonspecific. This case report suggests that SLE can occur in patients with MDS and that a concomitant autoimmune-thrombocytopenia may mask the typical signs of the 5q- syndrome.
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PMID:Autoimmune-thrombocytopenia and SLE in a patient with 5q-anomaly and deletion of the c-fms oncogene. 825 12

Autoimmune lupus nephritis is dependent on infiltrating autoreactive leukocytes and Igs. B7 costimulatory molecules (B7-1 and B7-2) provide signals essential for T cell activation and Ig class switching. In MRL-Faslpr mice, a model of human lupus, although multiple tissues are targeted for autoimmune injury, nephritis is fatal. We identified intrarenal B7-1 and B7-2 expression, restricted to kidney-infiltrating leukocytes, before and increasing with progressive nephritis in MRL-Faslpr mice. Thus, we hypothesized that the B7 pathway is required for autoimmune disease in MRL-Faslpr mice. To investigate the role of B7 costimulatory molecules in this autoimmune disease, we generated a MRL-Faslpr strain deficient in B7-1 and B7-2. Strikingly, MRL-Faslpr mice lacking both B7 costimulators do not develop kidney (glomerular, tubular, interstitial, vascular) pathology, or proteinuria, and survive far longer. Intrarenal downstream effector transcripts (IFN-gamma, IL-12, monocyte chemoattractant protein-1, CSF-1) linked to nephritis remained at normal levels compared with wild-type mice. Skin lesions and lymphoid enlargement characteristic of MRL-Faslpr mice were diminished in B7-1/B7-2-deficient MRL-Faslpr mice. B7-1/B7-2-deficient MRL-Faslpr mice did not develop leukocytic infiltrates, elevated serum IgG and isotypes (G1,G2b,G3), autoantibodies, and intrarenal IgG deposits. Our findings demonstrate that B7-1 and B7-2 costimulatory pathways are critical to the pathogenesis of autoimmune lupus.
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PMID:Costimulation by B7-1 and B7-2 is required for autoimmune disease in MRL-Faslpr mice. 1082 Feb 90

Cross-reactions of anti-human chorionic gonadotropin-beta (HCG-beta) antibody elicited by HCG-beta based antifertility vaccines with other autoantigens may occur due to identical or homologous protein subsequences. I have detected hitherto unreported identity of HCG-beta sequence with tetrapeptides of PECAM-1, galactosyl transferase-associated protein kinase, insulin receptor-related receptor and carboxypeptidase E. A predicted potential epitope of C-terminal peptide (CTP) of HCG-beta was identical to a tetrapeptide stretch of MCSF-1. The first 30 residue stretch of CTP was found to have yet unknown homologies of more than 56% with many auto-antigens including 60.1% with centromere protein C. The last 30 residue stretch of CTP was found for the first time to have 61.4-65.4% homology with subsequences of autoantigens SP-100, PM-SCL, D1 (64 kDa), lupus KU (p86), small nuclear ribonucleoprotein-associated proteins N, B and B', major centromere autoantigen B, centromere protein C, and dihydrolipoamide acetyl transferase component E2 of pyruvate, respectively.
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PMID:Predictions of Immunological Cross-Reactions of C-Terminal Peptide of Human Chorionic Gonadotropin beta-Chain Based Contraceptive Vaccine with Autoantigens. 1268 22

Infections are common in systemic lupus erythematosus (SLE), and remain a source of mortality. The types of infections (such as pneumonia, urinary tract infection, cellulitis, and sepsis) in SLE patients are similar to the general population and include the same pathogens (Gram-positive and Gram-negative). SLE patients may also develop opportunistic infections, especially when treated with immunosuppressive agents. As a high-risk population, identification and treatment of chronic infections such as tuberculosis, hepatitis B, or human immunodeficiency virus (HIV), are important prior to the institution of immunosuppression to prevent reactivation or exacerbation of the infection. A common caveat is to distinguish between a lupus flare and an acute infection; judicious use of corticosteroids and cytotoxic drugs is critical in limiting infectious complications. The risk factors associated with susceptibility to disease include severe flares, active renal disease, treatment with moderate or high doses of corticosteroids and/or immunosuppressive agents, and others. Genetic factors (complement deficiencies, mannose-binding lectin, Fcgamma III, granulocyte macrophage colony-stimulating factor [GM-CSF], osteopontin) may predispose certain SLE patients to develop infections. Parameters including C-reactive protein (CRP) and adhesion molecules may help to differentiate an infectious disease from an exacerbation of the disease. Finally, the mechanism of molecular mimicry by specific microbial agents may play a role in the induction of SLE.
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PMID:SLE and infections. 1279 59

Inflammation in the kidney and other tissues (lung, and salivary and lacrimal glands) is characteristic of MRL-Fas(lpr) mice with features of lupus. Macrophages (Mphi) are prominent in these tissues. Given that 1) Mphi survival, recruitment, proliferation, and activation during inflammation is dependent on CSF-1, 2) Mphi mediate renal resident cell apoptosis, and 3) CSF-1 is up-regulated in MRL-Fas(lpr) mice before, and during nephritis, we hypothesized that CSF-1-deficient MRL-Fas(lpr) mice would be protected from Mphi-mediated nephritis, and the systemic illness. To test this hypothesis, we compared CSF-1-deficient MRL-Fas(lpr) with wild-type strains. Renal pathology is suppressed and function improved in CSF-1-deficient MRL-Fas(lpr) mice. There are far fewer intrarenal Mphi and T cells in CSF-1-deficient MRL-Fas(lpr) vs wild-type kidneys. This leukocytic reduction results from suppressed infiltration, and intrarenal proliferation, but not enhanced apoptosis. The CSF-1-deficient MRL-Fas(lpr) kidneys remain preserved as indicated by greatly reduced indices of injury (nephritogenic cytokines, tubular apoptosis, and proliferation). The renal protective mechanism in CSF-1-deficient mice is not limited to reduced intrarenal leukocytes; circulating Igs and autoantibodies, and renal Ig deposits are decreased. This may result from enhanced B cell apoptosis and fewer B cells in CSF-1-deficient MRL-Fas(lpr) mice. Furthermore, the systemic illness including, skin, lung, and lacrimal and salivary glands pathology, lymphadenopathy, and splenomegaly are dramatically suppressed in CSF-1-deficient MRL-Fas(lpr) as compared with wild-type mice. These results indicate that CSF-1 is an attractive therapeutic target to combat Mphi-, T cell-, and B cell-mediated autoimmune lupus.
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PMID:Negative role of colony-stimulating factor-1 in macrophage, T cell, and B cell mediated autoimmune disease in MRL-Fas(lpr) mice. 1538 12

Mice from the MRL strain are prone to develop systemic lupus erythematosus (SLE) and have demonstrated accelerated wound healing and scarless tissue regeneration; however, many of the mechanisms involved in these clinically relevant pathologies are unclear. Prior studies have described macrophage accumulation and functional defects in mice prone to lupus. Monocyte-macrophages have also been shown to have a high degree of plasticity. To determine whether there might be innate differences in the hematopoietic systems of MRL mice, we evaluated hematopoietic progenitor cell content in a variety of tissues and the proliferative responses of derived marrow and thioglycolate (TG)-elicited peritoneal macrophages. Our experiments reveal that MRL mice have significantly lower numbers of circulating blood leukocytes and platelets. Even more strikingly, we found that MRL blood and marrow contain an unusually robust number of unique and assayable macrophage colony-stimulating factor responsive cells which have the characteristics of macrophage colony-forming cell precursors. In culture, in contrast to cells derived from control C57BL/6 mice, this cell type and thioglycolate-elicited peritoneal macrophages from MRL mice can be extensively expanded with just macrophage colony-stimulating factor to acquire an in situ "f-mac-like" (see Y. Zhao, D. Glesne and E. Huberman, A human peripheral blood monocyte-derived subset acts as pluripotent stem cells. Proc. Natl. Acad. Sci. U.S.A. 100, (2003) 2426-2431.) morphology when plated on plastic surfaces. Our results suggest that these increased numbers of macrophage progenitor cells and their potential differentiation plasticity may play a functional role in the onset of systemic lupus erythematosus and may also contribute to the accelerated and scarless tissue regenerative repair response observed in MRL mice.
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PMID:Mice with a regenerative wound healing capacity and an SLE autoimmune phenotype contain elevated numbers of circulating and marrow-derived macrophage progenitor cells. 1560 95

Bone marrow-derived mesenchymal stem cells (MSCs) are key components of the hematopoietic microenvironment and provide support to hematopoiesis and modulate immune system. Several studies suggest that SLE may be seen as stem cell disorders. However, it is unclear that whether MSCs from SLE patients are defective. So in this research, we studied the biological character of bone marrow derived MSCs in patients with SLE, focused on their phenotype (morphology and immunophenotype), karyotype, cytokines expression and hematopoietic support of MSCs. Our results showed that MSCs from SLE patients and normal controls can be successfully culture-expanded, but the MSCs from SLE grew more slowly than those of normal controls (P < 0.05). Cells from both groups were positive for CD29, CD44 and CD105, and negative for CD14, CD34, CD45 and HLA-DR. MSCs from SLE have a normal karyotype. Both groups express IL-6, IL7, IL-11, macrophage colony stimulating factor (M-CSF) and stem cell factor (SCF) at mRNA level. While IL-6 and IL-7 were down-regulated in MSCs from SLE patient (P < 0.05) at mRNA level. The MSCs from SLE patients and normal controls were infused into ICR (Tac: Icr: Ha strain) mice after high-dose chemotherapy, with no adverse events in either group. Recovery of white blood cells, hemoglobin and platelet was more rapid (P < 0.05) compared with the group without MSCs infusion. We conclude that MSCs in patient with SLE have abnormalities compared with those in normal control. MSCs in patient with SLE may play an important role in the SLE pathogenesis.
Lupus 2007
PMID:Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. 1740 68

A new entity was described by Crickx et al. in 1991, associating amicrobial pustulosis of the folds with systemic lupus erythematosus in young females. It is proposed to regroup this entity under the name of 'neutrophilic cutaneous lupus'. We report a case of a 13-year-old girl with a pustular eruption of the cutaneous folds and scalp associated with undetermined connective tissue disease. We performed a screening for the expression of 174 cytokines in the pustules and compared it with other pustular diseases (acne flare, acute generalized exanthematous pustulosis, pustulosis of Sneddon and Wilkinson). Matrix metalloproteinase 9 and Siglec-5 (CD170) were highly expressed in all types of pustules and reflect high neutrophil density. Amicrobial pustulosis of the folds was characterized by a higher expression of interleukin (IL) 1alpha, IL-2 receptor alpha, macrophage colony-stimulating factor, insulin-like growth factor binding protein 1, brain-derived neurotrophic factor, tumour necrosis factor (TNF) alpha and a lower expression of CD14, IL-1beta, IL-12, soluble TNF receptors I and II, growth-regulated oncogene alpha, fibroblast growth factor 4 and vascular endothelial growth factor as compared to the controls.
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PMID:Amicrobial pustulosis of the folds associated with auto-immune disorders. A case report with an analysis of cytokine expression profile in skin lesions of cutaneous neutrophilic lupus. 1823 Sep 75


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