RESUMEN
Integrin α(D)ß(2) is the most recently identified member of the leukocyte, or ß(2), subfamily of integrin heterodimers. Its distribution and functions on human leukocytes have not been clearly defined and are controversial. We examined these issues and found that α(D)ß(2) is prominently expressed by leukocytes in whole blood from healthy human subjects, including most polymorphonuclear leukocytes and monocytes. We also found that α(D)ß(2) is displayed by leukocytes in the alveoli of uninjured and inflamed human lungs and by human monocyte-derived macrophages and dendritic cells, indicating broad myeloid expression. Using freshly-isolated human monocytes, we found that α(D)ß(2) delivers outside-in signals to pathways that regulate cell spreading and gene expression. Screening expression analysis followed by validation of candidate transcripts demonstrated that engagement of α(D)ß(2) induces mRNAs encoding inflammatory chemokines and cytokines and secretion of their protein products. Thus, α(D)ß(2) is a major member of the integrin repertoire of both circulating and tissue myeloid leukocytes in humans. Its broad expression and capacity for outside-in signaling indicate that it is likely to have important functions in clinical syndromes of infection, inflammation, and tissue injury.
Asunto(s)
Antígenos CD11/metabolismo , Inflamación/metabolismo , Cadenas alfa de Integrinas/metabolismo , Leucocitos/metabolismo , Transducción de Señal , Diferenciación Celular , Citometría de Flujo , HumanosRESUMEN
Platelets are the chief effector cells in hemostasis and have additional major functions in inflammation, vascular integrity, and tissue repair. Platelets and the lungs have interrelated activities. Previous studies provide evidence that platelets contribute to pulmonary vascular barrier function and are required for defense against pulmonary hemorrhage, and that the lungs can influence platelet number and distribution. There is also evidence that platelets contribute to pathologic syndromes of pulmonary inflammation and thrombosis. Thus, platelets have an "amicus or adversary" relationship with the lung. Recent observations and discoveries have established new paradigms relevant to influences of platelets on lung cell and molecular biology. These new findings are in a variety of areas including thrombopoieis, nontraditional activities of platelets, new synthetic capabilities and mechanisms of post-translational gene expression, interactions of platelets with endothelial cells and contributions to alveolar capillary barrier permeability, interactions of platelets with myeloid leukocytes, and platelet involvement in stem cell signaling and vascular repair. These issues are considered in a translational approach, with an emphasis on acute lung injury and the acute respiratory distress syndrome.