Plexin-B2 Negatively Regulates Macrophage Motility, Rac, and Cdc42 Activation

Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2−/− macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2−/− macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing

Dessaturação noturna: preditores e influência no padrão do sono de pacientes portadores de doença pulmonar obstrutiva crônica com hipoxemia leve em vigília Nocturnal desaturation: predictors and the effect on sleep patterns in patients with chronic obstructive pulmonary disease and concomitant mild daytime hypoxemia

OBJETIVO: Verificar o padrão da oximetria noturna em portadores de doença pulmonar obstrutiva crônica sem apnéia do sono e com hipoxemia leve em vigília, identificar prováveis parâmetros diurnos capazes de predizer a dessaturação noturna e verificar sua influência no padrão de sono. MÉTODOS: Avaliaram-se 25 pacientes, divididos em dois grupos: com e sem dessaturação noturna. RESULTADOS: Comparando-se o primeiro grupo (52%) com o segundo observou-se: idade, 63 &plusmn; 5 versus 63 &plusmn; 6 anos; volume expiratório forçado no primeiro segundo, 53 &plusmn; 31% versus 56 &plusmn; 19% do previsto; relação entre volume expiratório forçado no primeiro segundo e capacidade vital forçada, 49 &plusmn; 14% versus 52 &plusmn; 10%; pressão parcial de oxigênio no sangue arterial, 68 &plusmn; 8mmHg versus 72 &plusmn; 68mmHg; saturação arterial de oxigênio, 93 &plusmn; 2% versus 94 &plusmn; 1%. O grupo com dessaturação noturna apresentou menores valores de saturação arterial de oxigênio diurna e saturação periférica de oxigênio noturna. Não houve diferença no padrão de sono entre os grupos. Houve correlação da relação entre o volume expiratório forçado no primeiro segundo e a capacidade vital forçada, pressão parcial de oxigênio no sangue arterial e saturação arterial de oxigênio diurnas, e saturação periférica de oxigênio no exercício com os níveis de saturação periférica de oxigênio noturna, porém somente a saturação arterial de oxigênio diurna foi preditora da dessaturação noturna. CONCLUSÃO: A única variável capaz de predizer dessaturação noturna foi a saturação arterial de oxigênio diurna. A dessaturação noturna não influencia o padrão de sono de portadores de doença pulmonar obstrutiva crônica com hipoxemia diurna leve.<br>OBJECTIVE: To determine the nocturnal oximetry pattern in chronic obstructive pulmonary disease patients having no sleep apnea and presenting mild daytime hypoxemia, to identify probable daytime parameters capable of predicting nocturnal desaturation, and to evaluate the influence of nocturnal desaturation on the sleep pattern of these patients. METHODS: Twenty-five patients were divided into two groups: those with nocturnal desaturation and those without. RESULTS: Comparing the first group (52%) with the second, we found the following: age, 63 &plusmn; 5 years versus 63 &plusmn; 6 years; forced expiratory volume in the first second = 53 &plusmn; 31% versus 56 &plusmn; 19% predicted; ratio of forced expiratory volume in the first second to forced vital capacity, 49 &plusmn; 14% versus 52 &plusmn; 10%; arterial oxygen tension, 68 &plusmn; 8 mmHg versus 72 &plusmn; 68 mmHg; and arterial oxygen saturation, 93 &plusmn; 2% versus 94 &plusmn; 1%. Patients in the nocturnal desaturation group presented lower daytime arterial oxygen saturation and nocturnal arterial oxygen saturation by pulse oximetry. There was no difference between the two groups in terms of the sleep patterns observed. The ratio of forced expiratory volume in the first second to forced vital capacity was found to correlate with forced vital capacity, daytime arterial oxygen tension and daytime arterial oxygen saturation. In addition, arterial oxygen saturation by pulse oximetry during exercise was found to correlate with nocturnal arterial oxygen saturation by pulse oximetry. However, only daytime arterial oxygen saturation was predictive of nocturnal desaturation. CONCLUSION: The only variable capable of predicting nocturnal desaturation was daytime arterial oxygen saturation. Nocturnal desaturation did not influence the sleep patterns of patients with chronic obstructive pulmonary disease accompanied by mild daytime hypoxemia