Hypogelsolinemia and Decrease in Blood Plasma Sphingosine-1-Phosphate in Patients Diagnosed with Severe Acute Pancreatitis

Abstract

Background Acute pancreatitis (AP) is a frequent hospitalization cause of patients suffering from gastrointestinal disorders. Gelsolin has an ability to bind bioactive lipids including different sphingolipids engaged in inflammatory response. Importantly, hypogelsolinemia was observed in patients with different states of acute and chronic inflammation. Aims The aim of the present study was to assess the interplay of blood plasma gelsolin and blood plasma sphingosine-1-phosphate (S1P) concentration in patients diagnosed with acute pancreatitis. Materials and Methods To assess the concentration of gelsolin and S1P, immunoblotting and HPLC technique were employed, respectively. Additionally, the concentrations of amylase, lipase, C-reactive protein (CRP), procalcitonin (PCT) and the number of white blood cells (WBC) and platelet (PLT) were recorded. Results We found that both pGSN and S1P concentrations in the plasma of the AP patients were significantly lower (pGSN ~ 15–165 mg/L; S1P ~ 100–360 pmol/mL) when compared to the levels of pGSN and S1P in a control group (pGSN ~ 130–240 mg/L; S1P ~ 260–400 pmol/mL). Additionally, higher concentrations of CRP, WBC, amylase and lipase were associated with low level of gelsolin in the blood of AP patients. No correlations between the level of PCT and PLT with gelsolin concentration were noticed. Conclusion Plasma gelsolin and S1P levels decrease during severe acute pancreatitis. Simultaneous assessment of pGSN and S1P can be useful in development of more accurate diagnostic strategies for patients with severe acute pancreatitis.

Emerging roles of plasma gelsolin in tumorigenesis and modulating the tumor microenvironment

“… 15 Apart from its role in sequestering actin in extracellular compartments, pGSN is also known to neutralize lipoteichoic acid (LTA) and LPS from Gram‐positive and Gram‐negative bacteria, respectively, thereby preventing the acute inflammatory response resulting from activation of TLRs (left, Figure 2). 9,10,16 Indeed, abnormally low level of pGSN is observed in patients with acute or chronic inflammation such as sepsis, 17 pneumonia, 18 and pancreatitis 19 . Notably, pGSN was demonstrated to bind to sphingosine 1‐phosphate (S1P), 20 a pleiotropic bioactive lysosphingolipid involved in various immune responses and angiogenesis 21 .…”

“…9,10,16 Indeed, abnormally low level of pGSN is observed in patients with acute or chronic inflammation such as sepsis, 17 pneumonia, 18 and pancreatitis. 19 Notably, pGSN was demonstrated to bind to sphingosine 1-phosphate (S1P), 20 a pleiotropic bioactive lysosphingolipid involved in various immune responses and angiogenesis. 21 Experimental and clinical studies have reported the correlation between pGSN and S1P expression level in inflammatory diseases, 19,22 and the treatment of recombinant pGSN was demonstrated to reduce the S1P-induced release of Interleukin 6 (IL-6), 23 indicating the importance of pGSN in maintaining immunomodulatory balance through its interaction with S1P.…”

“…19 Notably, pGSN was demonstrated to bind to sphingosine 1-phosphate (S1P), 20 a pleiotropic bioactive lysosphingolipid involved in various immune responses and angiogenesis. 21 Experimental and clinical studies have reported the correlation between pGSN and S1P expression level in inflammatory diseases, 19,22 and the treatment of recombinant pGSN was demonstrated to reduce the S1P-induced release of Interleukin 6 (IL-6), 23 indicating the importance of pGSN in maintaining immunomodulatory balance through its interaction with S1P. In addition, the recombinant pGSN treatment in septic mice can significantly shift the cytokine profile by reducing several pro-inflammatory cytokines (granulocytemacrophage colony-stimulating factor (GM-CSF), interferon -γ (IFN-γ), and IL-1β), while increasing anti-inflammatory IL-10 plasma level.…”

Targeting the Gut Microbiota to Relieve the Symptoms of Irritable Bowel Syndrome

“…On the molecular level, development of IBS was reported to be associated with the disruptions in antimicrobial peptides levels, particularly defensins [16][17][18] or altered expression of secondary messengers, such as sphingosine-1-phosphate (S1P) [19,20]. Particularly, disruption of S1P was proposed as an alternative approach in the IBD (inflammatory bowel disease) treatment [19] and other inflammation-associated medical conditions [21]. IBS is diagnosed more often in women than in men; it was noticed to be lower in the group aged 50 years and older (OR: 0.75; 95% CI 0.62-0.92) than in the group younger than 50 years old [22].…”