RESUMO
Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.
Assuntos
Apoptose , Vesícula/patologia , Eosinófilos/patologia , Penfigoide Bolhoso/patologia , Pele/patologia , Antígenos CD/sangue , Antígenos de Diferenciação de Linfócitos T/sangue , Biomarcadores/sangue , Vesícula/sangue , Vesícula/imunologia , Antígeno CD11b/sangue , Estudos de Casos e Controles , Caspase 3/metabolismo , Quimiocina CCL26 , Quimiocinas CC/metabolismo , Eosinófilos/imunologia , Eosinófilos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lectinas Tipo C/sangue , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/imunologia , Pele/imunologia , Pele/metabolismo , Receptor fas/metabolismoAssuntos
Antígeno B7-H1/sangue , Mastocitose/sangue , Proteína 2 Ligante de Morte Celular Programada 1/sangue , Receptor de Morte Celular Programada 1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mastocitose/imunologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Pele/imunologia , Triptases/sangue , Triptases/imunologiaAssuntos
Interleucinas/sangue , Mastocitose/sangue , Triptases/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Little is known about the effect of neuropeptides on basophils, which are important effector cells in immune and allergic responses. OBJECTIVE: This study aimed at revealing the role of α-melanocyte-stimulating hormone (α-MSH) on basophil function. METHODS: Expression of melanocortin receptors and proopiomelanocortin (POMC) was analyzed by means of RT-PCR, Western immunoblotting, fluorescence-activated cell sorting, and double-immunofluorescence analysis. Signal transduction studies included cyclic AMP and Ca(2+) mobilization assays. Basophil activity was assessed based on CD63 surface expression and cytokine release. RESULTS: MC-1R expression was detectable in basophils isolated from human peripheral blood, as well as in basophils within nasal tissue. In isolated basophils from human blood, truncated POMC transcripts were present, but there was no POMC protein. Treatment of basophils with α-MSH increased intracellular Ca(2+) but not cyclic AMP levels. α-MSH at physiologic doses potently suppressed basophil activation induced by N-formyl-methionyl-leucyl-phenylalanine, phorbol 12-myristate 13-acetate, or grass pollen allergen in whole blood of healthy or allergic subjects, respectively. The effect of α-MSH on basophil activation was MC-1R mediated (as shown by blockade with a peptide analogue of agouti-signaling protein) and imitated by adrenocorticotropic hormone but not elicited by the tripeptides KPV and KdPT, both of which lack the central pharmacophore of α-MSH. Moreover, α-MSH at physiologic doses significantly suppressed secretion of 3 proallergic cytokines, IL-4, IL-6, and IL-13, in basophils stimulated with anti-IgE, N-formyl-methionyl-leucyl-phenylalanine, or phorbol 12-myristate 13-acetate. CONCLUSION: Our findings highlight a novel functional activity of α-MSH, which acts as a natural antiallergic basophil-response modifier. These findings might point to novel therapeutic strategies in treating allergic diseases.