Macrophages: supportive cells for tissue repair and regeneration.

International audienceMacrophages, and more broadly inflammation, have been considered for a long time as bad markers of tissue homeostasis. However, if it is indisputable that macrophages are associated with many diseases in a deleterious way, new roles have emerged, showing beneficial properties of macrophages during tissue repair and regeneration. This discrepancy is likely due to the high plasticity of macrophages, which may exhibit a wide range of phenotypes and functions depending on their environment. Therefore, regardless of their role in immunity, macrophages play a myriad of roles in the maintenance and recovery of tissue homeostasis. They take a major part in the resolution of inflammation. They also exert various effects of parenchymal cells, including stem and progenitor cell, of which they regulate the fate. In the present review, few examples from various tissues are presented to illustrate that, beyond their specific properties in a given tissue, common features have been described that sustain a role of macrophages in the recovery and maintenance of tissue homeostasis

Functional Crosstalk between Type I and II Interferon through the Regulated Expression of STAT1

Small "priming" quantities of type I interferon enhance cellular responses to type II interferon by maintaining basal levels of STAT1, explaining the observed crosstalk between these two cytokines

Stat1 Phosphorylation Determines Ras Oncogenicity by Regulating p27Kip1

Inactivation of p27Kip1 is implicated in tumorigenesis and has both prognostic and treatment-predictive values for many types of human cancer. The transcription factor Stat1 is essential for innate immunity and tumor immunosurveillance through its ability to act downstream of interferons. Herein, we demonstrate that Stat1 functions as a suppressor of Ras transformation independently of an interferon response. Inhibition of Ras transformation and tumorigenesis requires the phosphorylation of Stat1 at tyrosine 701 but is independent of Stat1 phosphorylation at serine 727. Stat1 induces p27Kip1 expression in Ras transformed cells at the transcriptional level through mechanisms that depend on Stat1 phosphorylation at tyrosine 701 and activation of Stat3. The tumor suppressor properties of Stat1 in Ras transformation are reversed by the inactivation of p27Kip1. Our work reveals a novel functional link between Stat1 and p27Kip1, which act in coordination to suppress the oncogenic properties of activated Ras. It also supports the notion that evaluation of Stat1 phosphorylation in human tumors may prove a reliable prognostic factor for patient outcome and a predictor of treatment response to anticancer therapies aimed at activating Stat1 and its downstream effectors

Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-γ

Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity

Atmospheric ozone concentration at Athens, Greece. Part I: Surface ozone and its relationship with meteorological parameters

Daily measurements of surface [O-3] and [NOx] from five stations in the Greater Athens Basin, over the period 1987-1988 are used in order to examine the main features of basin-wide O-3-HC-NOx relationships. A simple regression model between the surface ozone concentration and the temperature at the 850 hPa level which was first tested in Los Angeles gave satisfactory results in reproducing the mean monthly ozone variation in Athens, when coefficients extracted from local data were used in the regression equation

Influence of the lateral boundaries and background concentrations on limited area photochemical model simulations

In this study an attempt was made to investigate the influence of the lateral boundaries and the background concentrations, on the predicted air pollutants' concentrations, as calculated by limited area, grid-based photochemical models. This influence is more pronounced in the case of mesoscale applications because of the limited domain. The lateral boundaries should be defined in such a way as to take into account the recirculation phenomena which occur as a result of the interaction of different scale atmospheric circulations. In addition, the influence of air pollutant sources located near the domain boundaries (inside or outside), on the concentrations of the photochemical pollutants inside the domain have to be considered. In this study the UAM-IV photochemical model has been implemented and simulations have been performed over the Athens Basin. It was found that the concentrations of the photochemical oxidants are mainly affected by the lateral boundary conditions, while the influence of the background is evident in the first hours of the simulation

The role of anthropogenic and biogenic emissions on tropospheric ozone formation over Greece

In the frame of this work, the sensitivity of a grid-based photochemical model on the emission inventory is examined. More precisely, the role of various emission categories on simulated oxidant formation is investigated and especially the biogenic ones. Special emphasis is given on the investigation of the role of the biogenic emissions on tropospheric ozone formation over areas with significant anthropogenic sources. The area of interest is the SE part of the Greek Peninsula where there are various types of anthropogenic pollutant sources and important biogenic sources from forest areas. Ozone air quality simulations were performed using the combined system of the atmospheric model RAMS and the photochemical model UAM. The simulations revealed that there is a significant increase of the calculated ozone concentrations over areas with significant precursor sources when biogenic emissions are taken into account. This increase is more pronounced during the days with a significant regional scale transport

Numerical simulations of the meteorological and dispersion conditions during an air pollution episode over Athens, Greece

In this study a summer air pollution episode from 6 to 8 August 1994 over Athens, Greece, is investigated through advanced atmospheric modeling. This episode was reported from the air quality monitoring network, as well as from research aircraft measurements performed during this period for the Transport and Transformation of Air Pollutants from Europe to the East Mediterranean region project. The meteorological conditions prevailing during the period 6-8 July 1994 are analyzed based on simulations performed with the Colorado State University-Regional Atmospheric Modeling System and on the available surface and upper-air observations. Indeed, the synoptic settings induced favorable conditions for the development of local-scale circulations, which defined the poor dispersion conditions over the area. The dispersion of the urban plume of Athens is studied with the use of the Hybrid Particle and Concentration Transport package model. The urban plume of Athens is tracked down the Saronic Gulf and the eastern coast of Peloponnisos, more than 200 km southward from the Athens Basin in good agreement with the research aircraft observations

Observational evidence of an ozone episode over the Greater Athens Area

Research flights have been performed over the Greater Athens Area (GAA) and southwards over the Island of Aegina and east of Peloponnisos in order to investigate the evolution of an ozone episode over GAA and the transportation of the urban pollution plume southwards from the Athens region. During the 3 day period of 6 July to 8 Jury 1994, the GAA was under the influence of an ozone episode with ground-level noontime concentrations of more than 120 ppbv. Upper-air ozone concentrations measured during the flights were as high as 135 ppbv. The interaction of the weak synoptic conditions over the area along with the development of a mesoscale thermal circulation created poor dispersion conditions during the period of interest and resulted in elevated ozone levels. The primary pollutants emitted in the GAA during the night and early morning hours, were funneled our to the Saronic Gulf and southwards along the southwestern Aegean Sea, near the coast of east Peloponnisos. Under the influence of strong sunlight these primary pollutants continued to undergo photochemical reaction giving rise to elevated ozone levels tens of kilometers downwind of the pollution emission sources. Further evidence of the photochemically-aged air masses was the high correlation (R-2=0.8) observed between NO, and ozone. The ozone production efficiency in these transported air masses reached a value of close to six. (C) 1997 Elsevier Science Ltd