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На экране Vivo CRISPR показано регулирование макрофажных состояний в нейроинфламмации.

Здесь мы создали скрининговый трубопровод в vivo CRISPR с использованием генетически отредактируемых клеток потомков для регулирования макрофага в мышиных моделях множественного склероза (MS). Скрининг более 100 цитокиновых рецепторов и сигнальных молекул выявила интерферон-Калайоки, некроз опухоли, гранулоцит-макропадажный фактор-стимулирующий фактор и преобразование фактора роста-β в основные регуляторы поляризации макрофага в vivo. Одноклеточная транскриптомика подтвердила, что перенесенные потомственные клетки генерируют все популяции миелиоидных клеток CNS, что позволяет проводить анализ

Совпадение в аннотации оригинала
Here we established an in vivo CRISPR screening pipeline using genetically editable progenitor cells to dissect macrophage regulation in mouse models of multiple sclerosis (MS). Screening over 100 cytokine receptors and signaling molecules identified interferon-γ, tumor necrosis factor, granulocyte-macrophage colony-stimulating factor and transforming growth…

Mice lacking Dok-1, Dok-2, and Dok-3 succumb to aggressive histiocytic sarcoma.

Histiocytic sarcoma (HS), a rare hematological malignancy, is an aggressive neoplasm that responds poorly to therapy. The molecular etiology … derived from Dok-1(-/-)Dok-2(-/-)Dok-3(-/-) mice displayed an exaggerated proliferative response to macrophage colony-stimulating factor (M-CSF) or granulocyte- macrophage colony-stimulating factor (GM-CSF) compared with WT and mutant controls. Together, these findings indicate that Dok-1, Dok-2, and Dok-3 cooperatively suppress aggressive HS, and commend Dok-1(-/-)Dok-2(-/-)Dok-3(-/ …

Transgenic mice as models of hemopoiesis.

A useful approach to establishing the biologic actions, in vivo, of granulocyte-macrophage colony-stimulating factor (GM-CSF) is to assess the consequences of long-term elevation of the factor in transgenic mice. Two lines of transgenic GM-CSF mice were analyzed. The major abnormality exhibited was an elevation in the number of macrophages, eosinophils, and polymorphs in the peritoneal and pleural cavities. Disease states exhibited by the lines were dependent on the insertion site of the GM-CSF gene. These disease states seem best explained on the basis of CSF-mediated macrophage activation an…

Pulmonary Alveolar Proteinosis: Rethinking Surfactant Homeostasis Through Alveolar Macrophage Lipid-Handling Dysfunction.

Pulmonary alveolar proteinosis is a rare lung disease characterized by the accumulation of surfactant lipids and proteins within the alveolar space, leading to impaired gas exchange and progressive respiratory dysfunction. In most cases, pulmonary alveolar proteinosis arises from disruption of GM-CSF (granulocyte-macrophage colony-stimulating factor) signaling, resulting in defective alveolar macrophage maturation and a failure of surfactant clearance. Emerging work has reframed pulmonary alveolar proteinosis as a disorder of macrophage lipid handling, linking impaired cholesterol efflux and s…

Osteoclasts; culprits in inflammatory osteolysis.

Periarticular osteolysis, a crippling complication of rheumatoid arthritis, is the product of enhanced osteoclast recruitment and activation. The osteoclast, which is a member of the monocyte/macrophage family, is the exclusive bone resorptive cell, and its differentiation and activation are under the aegis of a variety of cytokines. Receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor are the essential osteoclastogenic cytokines and are increased in inflammatory joint disease. Tumor necrosis factor-alpha, which perpetrates arthritic bone loss, exerts its ost…

Pulmonary toxicity associated with nitric oxide in term infants with severe respiratory failure.

We prospectively analyzed airway specimens from 24 newborn infants. Inhaled nitric oxide (< or = 20 ppm for 1 to 4 days to 12 infants) did not affect the concentrations of the lipid peroxidation product, the surface activity, or the cytokines (interleukin-1, granulocyte-macrophage colony-stimulating factor, interleukin-1 receptor antagonist). Nitrotyrosine was detected after 10 days of life in the two infants requiring prolonged ventilation, suggesting toxicity of endogenous nitric oxide.

Osteopetrosis mimicking juvenile myelomonocytic leukemia.

A 5-month-old boy developed splenomegaly, anemia, thrombocytopenia with elevated white cells, monocytosis and immature granulocytes in the peripheral blood. Bone marrow showed dysplasia without blastosis. Increased colony-forming unit-granulocyte-macrophage was found in the peripheral blood, mimicking granulocyte-macrophage colony-stimulating factor hypersensitivity. These findings fulfilled the diagnosis criteria for juvenile myelomonocytic leukemia (JMML), but no mutations in the CBL, NRAS, KRAS, or PTPN11 genes were detected. In addition to these findings severe hypogammaglobulinemia and el…

Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells.

We have recently purified murine granulocyte colony-stimulating factor (G-CSF), a regulatory glycoprotein which stimulates granulocyte colony formation from committed murine precursor cells in semi-solid agar cultures. G-CSF is one of a family of colony-stimulating factors that regulate the growth and differentiation of granulocytes and macrophages. While the other murine CSFs (granulocyte-macrophage (GM)-CSF, macrophage (M)-CSF and multi-CSF) show little or no differentiation-inducing activity on murine myelomonocytic leukaemia cell lines, G-CSF (or MGI-2(6)) is able to induce the production

Endogenous lipoid pneumonia preceding diagnosis of pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is an under-reported and under-diagnosed condition, with a high percentage of cases found on autopsy or late stage disease. The etiology of PAP includes genetic, primary (anti-granulocyte-macrophage colony-stimulating factor antibodies) and secondary (oncologic, rheumatologic, infectious, chemical and immunologic) causes. Here, we present the first reported pediatric case of endogenous lipoid pneumonia and non-specific interstitial pneumonitis preceding the development of PAP.

Innovative medical management with resection for successful treatment of pulmonary mucormycosis despite diagnostic delay.

We present a case of primary pulmonary mucormycosis infection in a renal transplant recipient diagnosed serendipitously by computed tomography scan. Treatment included discontinuation of immunosuppressive regimen, initiation of antifungal therapy with amphotericin B lipid complex, administration of granulocyte-macrophage colony stimulating factor, surgical excision of the involved lobe, and outpatient treatment with amphotericin B with dialysis. The patient ultimately required transplant nephrectomy as a result of immunosuppression discontinuation.

Biology and therapeutic uses of myeloid hematopoietic growth factors and interferons.

Recent advances in basic science and clinical trials have demonstrated that IFNs and myeloid hematopoietins play crucial roles in host defense against pathogens and immune surveillance. Here we have reviewed the biologic functions of GM-CSF, G-CSF, IFN-alpha and IFN-gamma. For patients with neutropenia resulting from cytotoxic chemotherapy, bone marrow transplantation, congenital agranulocytosis and cyclic neutropenia, therapeutic uses of GM-CSF and G-CSF were reviewed. Application of these growth factors to patient management represents a major contribution of biotechnology to a difficult are

Effect of PI3K-p110α Inhibitor Alpelisib in the Differentiation and Effector Functions of M-CSF and GM-CSF Macrophages.

Phosphatidylinositol-3-kinases (PI3Ks) are heterodimers of catalytic and regulatory subunits that regulate cell metabolism, activation, and … p110α, p110β, p110δ, p110γ and p85) in bone marrow monocytes and in macrophages differentiated with macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). However, alpelisib increased p110α, p110β, and p85 relative gene expression (2-3-fold) during M-CSF-dependent differentiation. Functionally, alpelisib-treated M-CSF macrophages di …

Differential effect of continuous versus cyclic maintenance chemotherapy on cytokine-induced myeloid colony growth.

Myeloid colony growth by bone marrow cells obtained from pediatric cancer patients was stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interleukin 1 (IL-1). Although patients recovering from cyclic high-dose chemotherapy showed normal colony growth in response to GM-CSF, patients with acute lymphoblastic leukemia (ALL) receiving continuous maintenance chemotherapy at moderate dose had variable but often severe decreases in myeloid colony growth compared with controls. Marrow from all patients and controls demonstrated enhanced colony growth in GM-CSF-stimulated c…

ORF3 of Hepatitis E Virus Inhibits the Expression of Proinflammatory Cytokines and Chemotactic Factors in LPS-Stimulated Human PMA-THP1 Cells by Inhibiting NF-κB Pathway.

Hepatitis E virus (HEV) is one of the primary causative agents of acute hepatitis. It is noteworthy that HEV can develop chronic infection a … ocyte chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF)] in lipopolysaccharide (LPS)-stimulated human PMA-THP1 cells. Further study showed that mRNA and protein levels of pattern recognition receptors (PRRs), such as Toll-like receptor 4 (TLR4), TNF receptor-associated factor 6 (TRAF6), and nucl …

Serum cytokines, interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in oral disorders.

Serum levels of soluble intercellular adhesion molecule-1, soluble interleukin-2 receptor, and cytokines such as interleukin-3, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were examined in patients with oral disorders with 20 healthy persons used as control subjects. Patients studied included 30 with squamous cell carcinoma, 26 with oral lichen planus, 20 with recurrent aphthous ulcer, 19 with acute odontogenic bacterial infection, 16 with pseudomembranous candidiasis, and 16 with herpetic gingivostomatitis. Compared with leve…

Growth factor-assisted chemotherapy--the Manchester experience.

Stimulation of red cell production by erythropoietin and of granulocyte production by granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-CSF (GM-CSF) has been demonstrated in several clinical studies. The first study to show that a human CSF could be used to shorten the period of neutropenia and reduce the risk of serious infection following intensive combination chemotherapy was carried out in Manchester using G-CSF. The period of neutropenia was significantly shortenened (by a median of 80%) and the neutrophil count levels were restored and above normal by 14 days after

Cytokine-induced expression of transforming growth factor-alpha and the epidermal growth factor receptor in neonatal skin explants.

Hyperproliferative diseases of the epidermal keratinocytes, such as psoriasis vulgaris, are characterized by overexpression and altered dist … its receptor. Other cytokines (TNF-beta, IFN-beta, IL-1 alpha, IL-2, IL-3, IL-5, IL-6, granulocyte/macrophage colony-stimulating factor, and macrophage colony-stimulating factor) did not alter the expression patterns of EGF/TGF-alpha receptors or TGF-alpha in normal neonatal skin explants. These experiments demonstrate that specific cytokines known to be present in psoriatic lesions …

Possible association between adult T-cell leukemia/lymphoma and acute myeloid leukemia.

BACKGROUND: To the authors' knowledge, an association between adult T-cell leukemia/lymphoma (ATL) and acute myeloid leukemia (AML) has been … 1 was detected in ATL cells but not in AML cells in the six patients examined. The plasma levels of macrophage colony-stimulating factor (M-CSF), granulocyte-colony stimulating factor, and granulocyte-macrophage-colony stimulating factor (GM-CSF) were elevated in 3, 1, and 1, respectively, of the 4 patients examined at AML onset who had active ATL. In one case, the levels of several …

Progressive Fibrosing Lung Disease Treated With Nintedanib in a Patient With Long-Standing Autoimmune Pulmonary Alveolar Proteinosis: A Case Report.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) is caused by impaired surfactant clearance due to neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor. Although whole-lung lavage and inhaled granulocyte-macrophage colony-stimulating factor therapy are established treatment options, pulmonary fibrosis is increasingly recognized as a clinically relevant complication in a subset of patients with APAP. However, the clinical behavior of APAP-associated fibrosing lung disease and the role of antifibrotic therapy remain unclear. CASE PRESENTATION: A 54-ye…