Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human monocytes cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-13 for 7 days differentiate into cells with the morphology and function of dendritic cells (DC). We have investigated the effect of IL-10 on this differentiation pathway. In the presence of IL-10 cells did not develop DC morphology, did not express CD1a and had lower levels of MHC class II. IL-10 promoted the differentiation of large cells with the morphology, cytochemistry and membrane phenotype of macrophages, including staining for nonspecific esterase and high levels of CD14, CD16 and CD68. The effect of IL-10 was dose dependent and was best appreciated when the cytokine was added at the initiation of the culture, as addition on day 3 was less inhibitory. When added to already differentiated DC on day 6, IL-10 caused only a modest reduction of MHC class II and CD1a expression, and no acquisition of the macrophage markers CD14, CD16 and CD68. Prolonged incubation up to 5 days with IL-10 did not induce a shift of differentiated DC to macrophages. On the other hand, the macrophages obtained by culturing for 7 days with GM-CSF+IL-13+IL-10 did not shift to DC upon removal of IL-10 for up to 3 days. Thus, the effect of IL-10 on monocyte differentiation, occurs only at the precursor level and confers an irreversible phenotype. From a functional point of view, cells cultured in the presence of IL-10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin (TT) to specific T cell lines with much less efficiency than control DC. In contrast, IL-10-cultured DC showed 7 times greater endocytosis of FITC-dextran. This increased endocytosis was mostly mediated via the mannose receptor, as demonstrated by blocking with unlabeled mannose. In conclusion, IL-10 inhibits DC differentiation from monocytes and, in a substantial proportion of the cells, promotes the differentiation to mature macrophages. Intriguingly, IL-10 inhibits antigen presentation while it stimulates endocytic activity.
 ...
PMID:IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. 948 15

Interferon-alpha (IFN-alpha) (IFN-alpha2b) is an immunoregulatory cytokine that is presently used in a recombinant form for the treatment of tumours and chronic viral infection. However, its mechanism of action remains largely undefined. In this paper, we studied the effects of low doses of IFN-alpha (0-100 U/ml) on the generation of dendritic cells with granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumour necrosis factor (TNF)-alpha in cultures of human peripheral blood mononuclear cells (PBMCs). An addition of IFN-alpha to the PBMC cultures greatly increased the HLA class II and the CD86 expression on developing dendritic cells (DCs) during a 7-day culture period. When added at the initiation of the PBMC culture, as little as 10 U/ml dramatically increased the HLA class II and CD86 expression, with maximal effects observed between 50 and 100 U/ml in all PBMC preparations tested. Almost all of the nonadherent cells induced with added IFN-alpha possessed a phenotype of mature DCs, being CD1a(low), CD83+, HLA class IIhigh, CD86high, CD40high, and CD80low, while being negative for the monocyte/macrophage and lymphocyte markers. In contrast, the floating cells isolated from cultures grown without IFN-alpha were mostly immature DCs with a CD1a(high), CD83-, HLA class IIint/high, CD86low/int, CD80low phenotype. An addition of 50 U/ml IFN-alpha at the time of the culture initiation greatly increased both the number of mature DCs generated and their rate of appearance; by 3 days of culture, many large floating aggregates were present containing mature CD83+, CD1a(low) DCs, while much fewer aggregates of mature DCs were found without added IFN-alpha. Histochemical staining confirmed that the floating cells induced with IFN-alpha had typical DC features, including irregularly shaped nuclei, few cytoplasmic granules, and absent or diffuse perinuclear staining for esterase. Our results suggest that IFN-alpha is a potent accelerator of DC maturation in vitro. These effects on DC maturation may explain its clinical success in the treatment of cancer and viral infection as well as its ability to promote autoimmunity.
 ...
PMID:Low levels of interferon-alpha induce CD86 (B7.2) expression and accelerates dendritic cell maturation from human peripheral blood mononuclear cells. 1056 53

Monocytes/macrophages secrete various cytokines that induce proliferation of colony-forming unit granulocyte-macrophage (CFU-GM) in short-term assays. To determine whether macrophages also support proliferation of more primitive progenitors, i.e., cells that give rise to colony forming cells in a 5-week long-term culture (LTC), we established plastic-adherent macrophage layers from human peripheral blood (PB) and filgrastim (G-CSF)-mobilized progenitor cell collections in the presence of hydrocortisone, and compared these layers with bone marrow (BM) stroma regarding their suitability to support proliferation and differentiation of CD34+ BM and cord blood (CB) cells in 5-week LTCs. CD34+ cells were seeded onto irradiated macrophage and BM stromal layers, as well as without any preformed layer. After 5 weeks, colony formation (CFU-GM, BFU-E/CFU-E) and cell expansion were determined. CD34+ cells from BM and CB yielded more CFU-GM and total nucleated cells at 5 weeks in the presence of both types of adherent layer compared with cultures without a layer (p<0.05). For CD34+ BM cells, macrophage layers were superior to BM stroma in enhancing CFU-GM and CFU-E/BFU-E output (p < 0.05). In contrast, BM stroma was favorable compared with macrophages concerning nucleated cell expansion from CD34+ CB cells (p = 0.027). The macrophage nature of PB-derived adherent cells was confirmed immunocytochemically by positive staining for CD68, Ki-Mlp, CD31, CD54, inconstant staining for CD14, and negative staining for CD1a, CD3, CD15, CD34, and CD62E. Cytochemical reactions were positive for alpha-naphthyl acetate esterase and negative for peroxidase and periodic acid-Schiff, consistent with the immunophenotype. In conclusion, the results show that blood-derived macrophages support CFU-GM generation from CD34+ CB and BM progenitors for 5 weeks in vitro. Differential effects on proliferation and maturation of BM versus CB progenitors are discussed.
 ...
PMID:Blood-derived macrophage layers in the presence of hydrocortisone support myeloid progenitors in long-term cultures of CD34+ cord blood and bone marrow cells. 1074 16

Dendritic cells (DCs) are a heterogeneous population of cells of fundamental importance in initiating innate as well as specific immune responses. The identity and function of DCs in the cat are unknown, although they are likely pivotal in the response to infection. In this study, feline DCs were derived by 3-10-day culture of adherent blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) in the presence of IL 4 and GM-CSF. BMMC consistently yielded a greater number of DCs than PBMC, and there were fewer macrophages than DC from both compartments. DCs expressed a distinct constellation of surface molecules, which included CD1a, CD1b, and CD1c, CD11b, CD14, and 2-3-fold higher levels of MHC class I and II molecules than co-cultured macrophages or fresh blood monocytes. DCs displayed typical cytoplasmic processes, limited non-specific esterase activity, and acquired antigen by phagocytosis, pinocytosis, and binding to specific receptors. Cytokine-exposed cells induced proliferation of allogeneic lymphocytes. Thus, the cells derived by these culture conditions had markers and functions analogous to immature myeloid DCs. Availability of feline DCs will enable investigation of their role in infectious disease and their potential therapeutic application.
 ...
PMID:Immunophenotype and functional properties of feline dendritic cells derived from blood and bone marrow. 1452 31

A feline monocytic cell line was established from a venous blood sample obtained from a healthy male donor cat. The cloned cells, temporarily named FLMo/K02, were successively passaged in vitro with cell growth medium consisting of RPMI-1640 supplemented with 10% heat-inactivated fetal calf serum. Non-specific esterase and acid phosphatase, as marker enzymes, were clearly demonstrated by cytochemical examinations. The cells treated with allogeneic serum for two hours in advance showed enhanced reactivity to monoclonal antibodies, feline CD1a, canine CD11b, feline CD11c, canine CD11d, and feline MHC-II.
 ...
PMID:An established feline monocytic cell line. 1705 91

Pulmonary Langerhans' cell histiocytosis (PLCH) is a disease characterized by the occurrence of complex fibro-cellular interstitial lesions dominated by Langerhans' cells (LC), which occurs predominantly in young adult smokers. We undertook this retrospective study to better define the lymphohistiocytic cell populations in PLCH in order to obtain a greater insight into its pathogenesis. Formalin-fixed, paraffin-embedded, surgically excised, archival lung tissue from seven patients (two males, five females; average age 34.9 years) was immunostained with a panel of antibodies for lymphohistiocytic markers: CD1a, CD3, CD4, CD8, CD15, CD20, CD56, TIA-1, CD68-PGM1, Mac387, and mast cell tryptase. Double immunolabeling was performed with CD1a/Mac387. Leder cytochemical stain for chloroacetate esterase was also performed. A moderate number of lymphocytes, predominantly T lymphocytes, were scattered diffusely within the lesions. The mean CD4/CD8 ratio was 0.1/1. The CD3/CD8 ratio (1.18/1) substantiated the CD4/CD8 ratio. The CD8 subset was CD56-negative and TIA-1-positive, indicating a cytotoxic T lymphocyte phenotype. CD68-PGM1 was strongly positive in alveolar macrophages (AM) and weakly stained LC. Mac387, a marker of activated macrophages, weakly stained AM, while highlighting other interstitial cells. These interstitial cells appeared not to be LC (substantiated by CD1a/Mac387 dual labeling) or CD68-PGM-1-positive macrophages. Having excluded mast cells (positive with mast cell tryptase) and neutrophils (positive with CD15 and Leder stains), there appeared to be a residual population of non-Langerhans cell monocytoid cells (NLMC), which were Mac 387+, CD68-PGM1-, Mast cell tryptase-, CD15-, and CD1a-. Our results showed a predominance of CD8+, TIA-1+ cytotoxic T lymphocytes among the lymphocyte subsets which appear to interact with LC and AM in PLCH lesions. A small sub-population of NLMC was also present. Further studies are required to better define and to evaluate the role of cytotoxic T cells and NLMC in the pathogenesis of PLCH.
 ...
PMID:Lymphocyte sub-populations and non-Langerhans' cell monocytoid cells in pulmonary Langerhans' cell histiocytosis. 1833 20

The extracellular matrix plays a critical role in macrophage maturation. In this study, the HL60 cell line was used as a model of leukemic myeloid cell differentiation. We assessed the ability of HL60 cells cultured on fibronectin substratum prior to phorbol 12-myristate 13-acetate (PMA) induction to differentiate into terminally differentiated macrophages. Beside their distinctive macrophage morphology, they expressed antigen receptors CD14, TLR2, TLR4 and CD68, and displayed enhanced phagocytic activity and production of reactive oxygen species. Expression of CD13, CD33, CD15 and alpha-naphthyl-acetate esterase was also maintained, however, differentiated HL60 cells were HLA-DR and CD1a negative. Here, we describe the enhanced capacity of fibronectin-adherent HL60 cells to differentiate into macrophages in response to PMA.
 ...
PMID:Fibronectin promotes the phorbol 12-myristate 13-acetate-induced macrophage differentiation in myeloid leukemia cells. 1916 3

A 16-year-old neutered male Burmese cat was presented with a locally invasive nasal mass. The cytological and histological findings on incisional biopsy of this mass were suggestive of histiocytic sarcoma. Tumour cells expressed CD18, major histocompatibility complex class II, lysozyme and alpha-naphthyl acetate esterase; and lacked expression of CD3, CD79a, CD1a, CD1b, calprotectin, CD11c and E-cadherin. These findings are consistent with a myeloid-macrophage lineage. Metastasis to the bone marrow was present on necropsy examination. Histiocytic sarcoma should be considered in cats presented with primary round cell neoplasia of the nasal cavity.
 ...
PMID:Primary nasal histiocytic sarcoma of macrophage-myeloid cell type in a cat. 2252 Feb 53


<< Previous 1 2