Plasma fibronectin can affect the cytokine profile and monocytes/macrophages function in addition to predicting the prognosis of advanced sepsis

Abstract

The value of plasma fibronectin (pFN) in the diagnosis and prognosis of sepsis has not been fully established. Previous studies finding that pFN is significantly reduced in sepsis, however, whether reduced pFn affects the prognosis of sepsis has not been clarified. Here, we detected and analyzed pFN and other conventional inflammatory markers in advanced sepsis patients and performed correlation analysis with SOFA score. We also used Fn gene conditional knockout mice which were performed by cecum ligation and puncture (CLP) to investigate the effect of FN deficiency on sepsis prognosis. We found, compared with procalcitonin, c‐reactive protein, and interleukin‐6, pFN was more correlated with SOFA score in advanced sepsis patients (r −.720, p < .001). In animal experiments, Fn gene knockout mice showed significantly greater mortality after CLP compared with the control group because of inhibited phagocytosis and bacterial clearance ability of macrophages, with double cytokine storm. Furthermore, FN can regulate macrophages through the integrin α5β1/Fak/Src signaling pathway. Overall, we found pFN can more accurately reflect the severity and prognosis of advanced sepsis. The absence of FN altered the cytokine storm and phagocytic function of macrophages, suggesting that FN could be a potential therapeutic target in sepsis.

Ferroptosis in Macrophage Impairment in Sepsis

“…Generally speaking, macrophages can be classified according to their function and activation, i.e., M1 (classical activation) or M2 (alternative activation), but the time point at which macrophages differentiate into M1 type macrophages and M2 type macrophages is not clear. M1 macrophages are mainly composed of lipopolysaccharide (LPS) and/or interferon γ (interferon γ ), tumor necrosis factor α (tumor necrosis factor α ), and other cytokines [ 10 – 12 ]. M2 macrophages are mainly composed of IL-4 and transforming growth factor β (transforming growth factor β ) and immune complex induced activation [ 13 ].…”

Brain delivery of fibronectin through bioactive phosphorous dendrimers for Parkinson's disease treatment via cooperative modulation of microglia

“…Prior studies have shown that pre-adsorption or functionalization of FN on biological scaffolds can effectively reduce the expression of the macrophage inflammatory factor IL-1β [ 28 ]. Additionally, FN can significantly inhibit apoptosis of lipopolysaccharide (LPS)-stimulated mesenchymal stem cells-hepatocyte-like cells to improve liver function repair and enhance survival rates of LPS-induced severe combined immunodeficiency in vivo [ 29 , 30 ]. The anti-inflammatory and protective effects of FN are likely achieved through the inhibition of the nuclear factor-kappa B (NF-κB) pathway [ 31 ].…”