RESUMEN
Inflammation resolution is an active process that functions to restore tissue homeostasis. The participation of the plasminogen (Plg)/plasmin (Pla) system in the productive phase of inflammation is well known, but its involvement in the resolution phase remains unclear. Therefore, we aimed to investigate the potential role of Plg/Pla in key events during the resolution of acute inflammation and its underlying mechanisms. Plg/Pla injection into the pleural cavity of BALB/c mice induced a time-dependent influx of mononuclear cells that were primarily macrophages of anti-inflammatory (M2 [F4/80high Gr1- CD11bhigh]) and proresolving (Mres [F4/80med CD11blow]) phenotypes, without changing the number of macrophages with a proinflammatory profile (M1 [F4/80low Gr1+ CD11bmed]). Pleural injection of Plg/Pla also increased M2 markers (CD206 and arginase-1) and secretory products (transforming growth factor ß and interleukin-6) and decreased the expression of inducible nitric oxide synthase (M1 marker). During the resolving phase of lipopolysaccharide (LPS)-induced inflammation when resolving macrophages predominate, we found increased Plg expression and Pla activity, further supporting a link between the Plg/Pla system and key cellular events in resolution. Indeed, Plg or Pla given at the peak of inflammation promoted resolution by decreasing neutrophil numbers and increasing neutrophil apoptosis and efferocytosis in a serine-protease inhibitor-sensitive manner. Next, we confirmed the ability of Plg/Pla to both promote efferocytosis and override the prosurvival effect of LPS via annexin A1. These findings suggest that Plg and Pla regulate several key steps in inflammation resolution, namely, neutrophil apoptosis, macrophage reprogramming, and efferocytosis, which have a major impact on the establishment of an efficient resolution process.
Asunto(s)
Anexina A1/metabolismo , Reprogramación Celular , Fibrinolisina/metabolismo , Macrófagos/metabolismo , Plasminógeno/metabolismo , Enfermedad Aguda , Animales , Anexina A1/genética , Antígenos de Diferenciación/genética , Antígenos de Diferenciación/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/genética , Fibrinolisina/genética , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos/toxicidad , Macrófagos/patología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Neutrófilos/metabolismo , Neutrófilos/patología , Plasminógeno/genética , Células RAW 264.7RESUMEN
To assess the severity of oil spills on mangroves, diagnosis of the vegetation health is crucial. Some aspects of photosynthesis such as photochemical efficiency and leaf pigment composition together with the level of oxidative stress may constitute reliable indicators for vegetation health. To test this approach 14 month old Laguncularia racemosa were contaminated with 5 L m(-2) of the marine fuel oil MF-380 and treated with an oil degrading bacterial consortium in microcosms. Contamination resulted in a 20% decrease in shoot dry weight after 128 days. Photochemical efficiency, pigment content, catalase and ascorbate peroxidase remained unchanged. Multivariate ordination of DGGE microbial community fingerprints revealed a pronounced separation between the oil contaminated and the non-contaminated samples. Further studies are necessary before physiological parameters can be recommended as indicators for plant's health in oil polluted mangroves.