Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth

Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1+ precursors and postnatally from bone marrow–derived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche

Fibrinogen Like Protein 2 (FGL2): A Novel Regulator of Macrophage M1 Polarization

Fibrinogen-like protein 2 (FGL2) is a potent immunosuppressive molecule. The effects of FGL2 on macrophages, however, has not been studied. Peritoneal cell accumulation in fgl2-/-, fgl2+/+ and fgl2Tg mice in response to thioglycollate was measured. Significantly fewer cells were recovered from the peritoneal cavity of fgl2Tg mice compared to fgl2+/+ or fgl2-/- mice after thioglycollate injection. The difference in cell numbers was found to be due to decreased eosinophil accumulation in fgl2Tg mice. The effect of FGL2 on macrophage M1 and M2 polarization was next examined. IL-12 was significantly reduced in macrophages isolated from fgl2Tg mice. Addition of recombinant FGL2 protein to fgl2+/+ macrophages led to suppression of IL-12 production in a dose-dependent manner. Finally, Flow cytometric analysis of fgl2Tg macrophages revealed reduced expression of TLR4 as well as decreased phagocytosis. These data demonstrate that FGL2 inhibits the proinflammatory activity of macrophages and provides a rationale for developing anti-FGL2 therapies.M.Sc

Representing the Process of Believing in God and the Day of Judgment in Earthquake Resilience: A Qualitative Study

Due to the increase in natural disasters and their effects on people, the emphasis on the role of spiritual factors in dealing with them has increased; but research has not yet clearly explained these factors. The purpose of this study was to represent the process of showing belief in God and the Day of Judgment in the resilience of earthquake survivors in Sarpol-e Zahab. The method applied was qualitative and of the foundation data type. For this end, 27 earthquake survivors of Kermanshah were studied by purposive sampling method and using in-depth interviews. Data were collected, recorded and coded into the main categories and analyzed through Strauss and Corbin coding techniques, open coding, axial coding and selective coding. Based on the results, belief in God and the Day of Judgment were chosen as the main category. The causal conditions were knowledge and trust in God, belief in divine judgment and predestination, and the administration of justice. Unity and cohesion were chosen as the contextual conditions and religious activities as the mediating conditions. The strategies used by earthquake survivors to deal with the earthquake and its consequences were: altruism and modeling. Finally, acceptance and view of life as a means rather than an end was introduced as a consequence of this model. This study provided a clear picture of the processes, responses and recovery after disasters. The findings of this study can pave the way for creating effective and quick responses in disaster survivors

Hepatocellular injury after 60min of ischemia and 1, 6, 12 and 24hrs of reperfusion.

<p>Significant lower AST levels were found in the RGZ vs CTRL group at 1hr (3092±105 vs 4469±551; p = 0.042), 6hr (7041±1169 vs 12192±1443; p = 0.015) and 12hr (5746±328 vs 8609±1259; p = 0.049) after reperfusion (A). RGZ vs control group showed a trend to a significant difference at 6hrs post-reperfusion in ALT (9185±1754 vs 13823±1465; p = 0.054) (B). Abbreviations: AST-aspartate aminotransferase, ALT-alanine aminotransferase, RGZ-Rosiglitazone, CTRL-Control. Five experiments (n = 5) per group per time point were performed. Results are shown as mean ± SEM, Mann-Whitney U test.</p

Serum cytokines.

<p>Anti-inflammatory cytokine IL-10 was found with higher levels in RGZ vs CTRL group 12hrs (119.98±46.22 vs 76.66±19.73 pg/ml; p = 297) following IRI difference became significant at 24hr time-point (172.64±34.18 vs 34.18±6.89 pg/ml; p = 0.034) (A). TNF-alpha showed lower levels since 1hr after reperfusion difference that became significant 24hr (4.15±0.95 vs 18.08±2.35pg/ml; p = 0.013) after IRI (B). Serum IL-6 levels were similar for both groups at all time-points (C). Abbreviations: TNF-alpha Tumor necrosis factor, IL Interleukin, CTRL Control, RGZ Rosiglitazone. Five experiments (n = 5) per group per time point were performed. Results are shown as mean ± SEM, Mann-Whitney-U test.</p

Pro-inflammatory-NO+/ anti-inflammatory-CD206+ Kupffer cells ratio prior and after reperfusion.

<p>Pro-inflammatory-NO+/ anti-inflammatory-CD206+ KCs ratio was lower in the RGZ treated group at all the studied time points. Significant lower ratio was found in the RGZ vs CTRL group since 1hr after reperfusion group (3.45±0.32 vs 5.68±0.37; p = 0.001), this difference remained significant at 6hr (0.81±0.11 vs 4.63±0.79; 0.008) and 24hr (0.49±0.05 vs 2.66±0.46; p = 0.018) post-reperfusion. Abbreviations: CTRL control, RGZ Rosiglitazone. Five experiments (n = 5) per group per time point were performed. Results are shown as mean ± SEM, Mann-Whitney U test.</p

PPAR-γ antagonist-6hrs after reperfusion.

<p>Flow-cytometry shows how the effect on pro-inflammatory NO+ KC polarization was significantly blocked by the use of PPAR-γ antagonist (GW9662) (RGZ: 3.93±3.61%, RGZ+GW9662: 35.86±21.85%, Control: 31.12±21.42%, p = 0.009) (A). Serum AST levels were also significantly reversed when antagonist was included as an intervention (B). The grade of apoptosis was significantly increased with the use of antagonist in combination with RGZ when compared with RGZ alone (C). Abbreviations: DAF-FM 4-amino-5-methylamino-2’,7’-Difluoroflurescein, TUNEL-Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling, RGZ-Rosiglitazone, CTRL-Control. Five experiments (n = 5) per group per time point were performed. Results are shown as mean ± SEM, Mann-Whitney-U-test.</p

Hepatic necrosis.

<p>Representative pictures of the left lateral lobe with H&E staining showing a less necrotic area in the RGZ vs control group (A) 24hrs after reperfusion (26.66±4.78 vs 45.62±4.57%; p = 0.032). Image software analysis demonstrated that this difference was significant (B). Abbreviations: CTRL Control, RGZ Rosiglitazone. Five experiments (n = 5) per group per time point were performed. Results are shown as mean ± SEM, Mann-Whitney U test.</p