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

Extracellular adenosine 5'-triphosphate (ATPo) can induce pore formation in cell membranes, leading to cell permeabilization and eventual cell death. In this study, we examined the sensitivity of human epidermal Langerhans cells to ATP-induced permeabilization and tested the possibility that the Mg(++)- or Ca(++)-dependent plasma membrane ectonucleotidase (mATPase) on Langerhans cells provides protection against the cytotoxic effects of ATPo. Membrane permeability was assessed by using the fluorescent tracer propidium iodide, which confers red nuclear fluorescence to permeabilized cells. Langerhans cells were identified within human epidermal cell suspensions with fluorescein isothiocyanate-conjugated MoAb against CD1a or human leukocyte antigen-DR (HLA-DR) antigens. Cultured human keratinocytes and J774 macrophages were both highly sensitive to permeabilization induced by incubation with ATP (0.5 to 20 mM at 37 degrees C), whereas Langerhans cells were relatively resistant. The non-hydrolyzable ATP analog, adenosine 5'-(beta,gamma-imido) triphosphate, but not other nucleotides such as ADP, AMP, GTP, or UTP, was also able to induce permeabilization comparable to that of ATP, thereby suggesting that ATP hydrolysis is not required for this effect. ATP4- is the moiety most likely responsible for permeabilization, because propidium iodide uptake occurred only when the pH of the medium was > or = 7.4. Permeabilization induced by ATP was augmented by chelation of divalent cations with ethylene-diamine-tetraacetic acid and by the addition of lanthanum or cerium (0.01 to 1 mM). Finally, incubation with the adenosine analog, 5'-p-fluorosulfonylbenzoyl-adenosine (1 mM), inhibited mATPase staining of Langerhans cells in human epidermal sheets, but markedly augmented ATP-induced permeabilization of Langerhans cells. The results indicate that epidermal LC are resistant to the lytic effects of ATPo and that mATPase is involved in such resistance.
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PMID:Epidermal Langerhans cells are resistant to the permeabilizing effects of extracellular ATP: in vitro evidence supporting a protective role of membrane ATPase. 844 Sep 5

Dendritic cells (DC) are potent antigen-presenting cells capable of inducing T and B responses and immune tolerance. We have characterized some aspects of energy metabolism accompanying the differentiation process of human monocytes into DC. Compared to precursor monocytes, DC exhibited a much larger number of mitochondria and consistently (i) a higher endogenous respiratory activity and (ii) a more than sixfold increase in ATP content and an even larger increase in the activity of the mitochondrial marker enzyme citrate synthase. The presence in the culture medium of rotenone, an inhibitor of the respiratory chain Complex I, prevented the increase in mitochondrial number and ATP level, without affecting cell viability. Rotenone inhibited DC differentiation, as revealed by the observation that the expression of CD1a, which is a specific surface marker of DC differentiation, was strongly reduced. Cells cultured in the presence of rotenone displayed a lower content of growth factor-induced, mitochondrially generated, hydrogen peroxide. A similar drop in ROS was observed upon addition of catalase, which caused functional effects similar to those produced by rotenone treatment. These results suggest that ROS play a crucial role in DC differentiation and that mitochondria are an important source of ROS in this process.
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PMID:Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions. 1824 95

In contrast to its favourable effects on Langerhans cell (LC) differentiation, transforming growth factor (TGF)-beta1 has been reported to prevent dendritic cells from maturing in response to tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, or lipopolysaccharide (LPS). We first characterized the effects of TGF-beta1 on dendritic cell function by testing the response of TGF-beta1-treated monocyte-derived dendritic cells (MoDCs) to maturation stimuli that LCs receive in the epidermis, namely, haptens, ATP and ultraviolet (UV). TGF-beta1 treatment, which augmented E-cadherin and down-regulated dendritic cell-specific ICAM3-grabbing non-integrin on MoDCs, significantly suppressed their CD86 expression and hapten-induced expression of IL-1beta and TNF-alpha mRNA and protein. As TGF-beta1-treated MoDCs lacked Langerin expression, we demonstrated the suppressive effects of TGF-beta1 on haematopoietic progenitor cell-derived dendritic cells expressing both CD1a and Langerin. These suppressive effects of TGF-beta1 increased with the duration of treatment. Furthermore, TGF-beta1-treated MoDCs became resistant to apoptosis/necrosis induced by high hapten, ATP or UV doses. This was mainly attributable to dampened activation of p38 mitogen-activated protein kinase (MAPK) in TGF-beta1-treated MoDCs. Notably, although ATP or hapten alone could only induce CD86 expression weakly and could not augment the allogeneic T-cell stimulatory function of TGF-beta1-treated MoDCs, ATP and hapten synergized to stimulate these phenotypic and functional changes. Similarly, 2,4-dinitro, 1-chlorobenzene (DNCB) augmented the maturation of TGF-beta1-treated MoDCs upon co-culture with a keratinocyte cell line, in which ATP released by the hapten-stimulated keratinocytes synergized with the hapten to induce their maturation. These data may suggest that TGF-beta1 protects LCs from being overactivated by harmless environmental stimulation, while maintaining their ability to become activated in response to danger signals released by keratinocytes.
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PMID:TGF-beta1 dampens the susceptibility of dendritic cells to environmental stimulation, leading to the requirement for danger signals for activation. 1927 21