RESUMO
We investigated the role of the TNF receptors, type I (p55TNFR) and type II (p75TNFR), in a mouse model of contact hypersensitivity, i.e., a model of a delayed type hypersensitivity (DTH) allergic reaction. Mice deficient for p55TNFR or p75TNFR were used to investigate the functions of these receptors in development of the DTH reaction. We show that both TNF receptors have a strong influence on the overall outcome of the DTH reaction, with the two TNF receptors exerting distinct functions. Dendritic cells of mice lacking p55TNFR had a defect in allergen uptake but showed normal migration into regional lymph nodes. In contrast, dendritic cells of p75TNFR-deficient mice showed diminished migration into regional lymph nodes after allergen contact, whereas the allergen uptake was independent of the p75TNFR. Thus, both TNF receptors are required for the development of a complete DTH reaction.
Assuntos
Antígenos CD/metabolismo , Dermatite Alérgica de Contato/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose TumoralRESUMO
CD137 (ILA/4-1BB), a member of the TNF receptor family, regulates activation, survival and proliferation of primary human monocytes. Here we compare the activities of lipopolysaccharide (LPS), a classical and potent monocyte activator to that of CD137. LPS is a more potent activator of monocytes, as evidenced by a stronger induction of the proinflammatory cytokine IL-8. However, CD137 could further increase maximal cytokine induction by LPS, which points to separate signaling pathways for LPS and CD137. Also, expression of myc was only induced by the combination of CD137 and LPS. Expression of macrophage colony-stimulating factor is induced more potently by CD137, but an additive effect is obtained by the combination of CD137 and LPS. Monocyte/macrophage survival and proliferation is only induced by CD137. LPS counteracts both activities of CD137 via activation induced cell death. While LPS has a role in activation of monocytes in innate immunity, the CD137 receptor/ligand system seems to deliver an activating signal to monocyte in acquired immunity.
Assuntos
Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Monócitos/citologia , Monócitos/efeitos dos fármacos , Receptores de Fator de Crescimento Neural/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Antígenos CD , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Genes myc/genética , Humanos , Interleucina-8/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Fator de Crescimento Neural/antagonistas & inibidores , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membro 9 da Superfamília de Receptores de Fatores de Necrose TumoralRESUMO
Tumor necrosis factor (TNF) mediates its biological effects by binding to two distinct but homologous receptor molecules. The type 1 receptor (TNF-R1) has been shown to be essential and sufficient for most cellular responses to soluble TNF. In contrast, only limited data exist concerning the role of the type 2 receptor (TNF-R2) in TNF responses, both in vitro and in vivo. Here, we demonstrate by the use of thymocytes from TNF-R-deficient mice that the TNF-R2-dependent enhancement of proliferation and secretion of granulocyte-macrophage colony-stimulating factor is in fact mediated by TNF-R2 on its own, independent of co-expression and/or stimulation of TNF-R1.
Assuntos
Antígenos CD/fisiologia , Ativação Linfocitária , Receptores do Fator de Necrose Tumoral/fisiologia , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Concanavalina A/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Camundongos , Camundongos Knockout , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral , Proteínas Recombinantes/farmacologia , Linfócitos T/metabolismo , Timo/citologiaRESUMO
3 groups (6 control persons, 6 patients with liver cirrhosis, 6 patients with diabetes mellitus) were infused with 20% (w/v) carbohydrate mixture (glucose/fructose/xylitol, 1:2:1) for 48 hours. The metabolical status was controlled in defined intervals by means of 39 different laboratory parameters. The infusion rate was supposed to be 0.25 g carbohydrates/kg B. W. and hour. There were no significant changes in blood glucose levels in any of the 3 groups. However we could observe a slight but constant increase in lactate and triglyceride concentrations. Free fatty acids and keton bodies were suppressed on a low level. Only the diabetics showed a significant renal carbohydrate loss with up to 15% of the amount administered. No clinically relevant side effects were observed.
