RESUMO
BACKGROUND: Sphingosine-1-phosphate (S1P), a lysophospholipid released from inflammatory cells, causes cell migration by increasing cytokines and chemokines. This study was designed to determine whether S1P causes adherence of eosinophils to pulmonary endothelial cells via enhancement of adhesion molecule expression. METHODS: Expression of VCAM-1 and ICAM-1 was assessed by RT-PCR and Western blot analysis in human pulmonary microvasucular endothelial cells (HPMVECs). The number of adherent eosinophils to HPMVECs was calculated according to adhesion assay. RESULTS: Pre-treatment of HPMVECs with S1P increased mRNA and protein expression of VCAM-1, in contrast, did not dramatically increase those expression of ICAM-1. The maximal expression of these adhesion molecules in mRNA and protein was observed 4 and 8h after exposure to S1P, respectively. Pre-treatment with S1P also activated RhoA, a monomeric G protein; the ability of S1P to enhance the expression of VCAM-1 was attenuated by RhoA related inhibitors such as Y-27632, C3 exoenzyme, and GGTI-286. The effects of S1P on VCAM-1 were attenuated by pre-incubation with pertussis toxin, which catalyzes the ADP-ribosylation of G(i), a heterotrimeric G protein. After HPMVECs were treated with S1P, adhesion of human eosinophilic leukemic cell line (EoL-1) cells to HPMVECs was enhanced in a concentration-dependent manner. Augmented adherence of EoL-1 cells by S1P was also attenuated by Y-27632 and pertussis toxin. S1P causes adherence of eosinophils to pulmonary endothelium via RhoA activation. CONCLUSIONS: S1P may act as a lipid mediator in asthma. The RhoA/Rho-kinase pathway may be a therapeutic target for preventing eosinophil infiltration to the airway.
Assuntos
Eosinófilos/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Lisofosfolipídeos/farmacologia , Esfingosina/análogos & derivados , Molécula 1 de Adesão de Célula Vascular/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , ADP Ribose Transferases/farmacologia , Amidas/farmacologia , Toxinas Botulínicas/farmacologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/imunologia , Linhagem Celular , Endotélio Vascular/efeitos dos fármacos , Eosinófilos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/imunologia , Leucina/análogos & derivados , Leucina/farmacologia , Pulmão/patologia , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Esfingosina/farmacologia , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/imunologia , Proteína rhoA de Ligação ao GTP/imunologiaRESUMO
Aspergillus species causes a variety of pulmonary diseases, invasive pulmonary aspergillosis in severely immunocompromised patietnts, chronic pulmonary aspergillosis (CPA) in patients with chronic lung diseases and allergic bronchopulmonary aspergillosis in patients with hypersensitivity to Aspergillus antigens. There are many species of Aspergillus, however Aspergillus fumigatus is the most commonly encountered species. CPA is usually seen in patients with documented or suspected underlying lung diseases like cystic fibrosis, bronchiectasis, inactive tuberculosis, pulmonary fibrosis, sarcoidosis, previous lung section, of these, previous pulmonary tubercurosis is the most associated condition. Development of new antifungal agents, such as micafungin and voriconazole significantly affect the management and outcome of patients with CPA. This article reviews the clinical features, diagnosis, and treatment of CPA, and that provides recent advances in the CPA-related pathogenic factor.