Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In response to granulocyte-macrophage colony-stimulating factor plus tumor necrosis factor alpha, cord blood CD34+ hematopoietic progenitor cells differentiate along two unrelated dendritic cell (DC) pathways: (1) the Langerhans cells (LCs), which are characterized by the expression of CD1a, Birbeck granules, the Lag antigen, and E cadherin; and (2) CD14+ cell-derived DCs, characterized by the expression of CD1a, CD9, CD68, CD2, and factor XIIIa (Caux et al, J Exp Med 184:695, 1996). The present study investigates the functions of each population. Although the two populations are equally potent in stimulating naive CD45RA cord blood T cells through apparently identical mechanisms, each also displays specific activities. In particular CD14-derived DCs show a potent and long-lasting (from day 8 to day 13) antigen uptake activity (fluorescein isothiocyanate dextran or peroxidase) that is about 10-fold higher than that of CD1a+ cells, which is restricted to the immature stage (day 6). The antigen capture is exclusively mediated by receptors for mannose polymers. The high efficiency of antigen capture of CD14-derived cells is coregulated with the expression of nonspecific esterase activity, a tracer of lysosomial compartment. In contrast, the CD1a+ population never expresses nonspecific esterase activity. The most striking difference is the unique capacity of CD14-derived DCs to induce naive B cells to differentiate into IgM-secreting cells, in response to CD40 triggering and interleukin-2. Thus, although the two populations can allow T-cell priming, initiation of humoral responses might be preferentially regulated by the CD14-derived DCs. Altogether, those results show that different pathways of DC development might exist in vivo: (1) the LC type, which might be mainly involved in cellular immune responses, and (2) the CD14-derived DC related to dermal DCs or circulating blood DCs, which could be involved in humoral immune responses.
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PMID:CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to granulocyte-macrophage colony-stimulating factor plus tumor necrosis factor alpha: II. Functional analysis. 926 63

We have previously shown that thymic CD34+ cells have a very limited myeloid differentiation capacity and differentiate in vitro mostly into CD1a+-derived but not CD14+-derived dendritic cells (DC). Herein we characterized the human neonatal thymic DC extracted from the organ in relationship with the DC generated from CD34+ cells in situ. We show that in vivo thymic DC express E cadherin, CLA, CD4, CD38, CD40, CD44, and granulocyte-macrophage colony-stimulating factor-R (GM-CSF-R; CD116) but no CD1a. According to their morphology, functions, and surface staining they could be separated into two distinct subpopulations: mature HLA-DRhi, mostly interleukin-3-R (CD123)-negative cells, associated with thymocytes, some apoptotic, and expressed myeloid and activation markers but no lymphoid markers. In contrast, immature HLA-DR+ CD123hi CD36+ cells with monocytoid morphology lacked activation and myeloid antigens but expressed lymphoid antigens. The latter express pTalpha mRNA, which is also found in CD34+ thymocytes and in blood CD123hi DC further linking this subset to lymphoid DC. However, the DC generated from CD34+ thymic progenitors under standard conditions were pTalpha-negative. Thymic lymphoid DC showed similar phenotype and cytokine production profile as blood/tonsillar lymphoid DC but responded to GM-CSF, and at variance with them produced no or little type I interferon upon infection with viruses and did not induce a strict polarization of naive T cells into TH2 cells. Their function in the thymus remains therefore to be elucidated.
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PMID:Identification of mature and immature human thymic dendritic cells that differentially express HLA-DR and interleukin-3 receptor in vivo. 1112 51

Preclinical studies frequently lack predictive value for human conditions. Human cell-based disease models that reflect patient heterogeneity may reduce the high failure rates of preclinical research. Herein, we investigated the impact of primary cell age and body region on skin homeostasis, epidermal differentiation, and drug uptake. Fibroblasts derived from the breast skin of female 20- to 30-year-olds or 60- to 70-year-olds and fibroblasts from juvenile foreskin (<10 years old) were compared in cell monolayers and in reconstructed human skin (RHS). RHS containing aged fibroblasts differed from its juvenile and adult counterparts, especially in terms of the dermal extracellular matrix composition and interleukin-6 levels. The site from which the fibroblasts were derived appeared to alter fibroblast-keratinocyte crosstalk by affecting, among other things, the levels of granulocyte-macrophage colony-stimulating factor. Consequently, the epidermal expression of filaggrin and e-cadherin was increased in RHS containing breast skin fibroblasts, as were lipid levels in the stratum corneum. In conclusion, the region of the body from which fibroblasts are derived appears to affect the epidermal differentiation of RHS, while the age of the fibroblast donors determines the expression of proteins involved in wound healing. Emulating patient heterogeneity in preclinical studies might improve the treatment of age-related skin conditions.
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PMID:Fibroblast origin shapes tissue homeostasis, epidermal differentiation, and drug uptake. 3081 27