Inverse Association Between Circulating Monocyte-Platelet Complexes and Inflammation in Ulcerative Colitis Patients(Monocyte-)
Por:
Zamora, C, Canto, E, Nieto, JC, Garcia-Planella, E, Gordillo, J, Ortiz, MA, Suarez-Calvet, X, Perea, L, Julia, G, Juarez, C, Vidal, S
Publicada:
1 abr 2018
Resumen:
Background: Circulating monocytes from active ulcerative colitis (UC) patients produced high levels of tumor necrosis factor-alpha(TNF alpha) and interleukin(IL)-6 after Toll-like receptors (TLR) stimulation. Since platelets (PLT) can bind to leukocytes, thereby decreasing inflammatory cytokine production, UC patients may exhibit different levels of monocyte-platelet complexes depending on disease activity.
Methods: We compared among healthy donors, active (onset flare and relapse), and inactive UC patients the presence of circulating monocyte-platelet complexes (CD14+PLT+) and membrane CD162 expression by flow cytometry. Lipopolysaccharide-binding protein, TNF alpha, and IL-10 were compared by ELISA. Binding of CD14+PLT+ to human umbilical vein endothelial cells (HUVECs) were analyzed by immunofluorescence.
Results: Onset flare UC patients had the lowest levels of CD14+PLT+. Membrane CD162, crucial for the PLT binding, was downregulated only on monocytes from onset flare UC patients. Membrane CD162 expression on CD14+ cells inversely correlated with lipopolysaccharide binding protein levels. As an expected consequence, more CD14+PLT+ than CD14+PLT-from onset flare UC patients bound to activated HUVECs. TNFa tended to negatively correlate with CD14+PLT+ in relapse and inactive UC patients, whereas IL-10 positively correlated with CD14+PLT+ in all UC patients (r = -0.43, P = 0.1 and r = 0.61, P = 0.01, respectively). The anti-inflammatory role of PLT binding to monocytes was confirmed in cocultures of PLT and monocytes. These cocultures increased the percentage of CD14+PLT+ and IL-10 production, and decreased TNF alpha production. These anti-inflammatory effects were abolished when we blocked the binding of PLT with neutralizing anti-CD62P antibody.
Conclusions: Decreased CD162 expression associated with endotoxemia reduced the binding of PLT to monocytes through membrane CD162-CD62P, favoring the inflammatory response of onset flare UC patients.
Filiaciones:
Zamora, C:
Univ Autonoma Barcelona, Dept Immunol, Inst Recerca, Hosp Santa Creu & St Pau, Barcelona, Spain
Canto, E:
Univ Autonoma Barcelona, Dept Immunol, Inst Recerca, Hosp Santa Creu & St Pau, Barcelona, Spain
Nieto, JC:
Univ Autonoma Barcelona, Dept Immunol, Inst Recerca, Hosp Santa Creu & St Pau, Barcelona, Spain
Garcia-Planella, E:
Hosp Santa Creu & Sant Pau, Gastroenterol & Hepatol Unit, Barcelona, Spain
Gordillo, J:
Hosp Santa Creu & Sant Pau, Gastroenterol & Hepatol Unit, Barcelona, Spain
Ortiz, MA:
Univ Autonoma Barcelona, Dept Immunol, Inst Recerca, Hosp Santa Creu & St Pau, Barcelona, Spain
Suarez-Calvet, X:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain
Univ Autonoma Barcelona, Inst Recerca St Pau, Barcelona, Spain
Perea, L:
Univ Autonoma Barcelona, Dept Immunol, Inst Recerca, Hosp Santa Creu & St Pau, Barcelona, Spain
Julia, G:
Univ Autonoma Barcelona, Dept Immunol, Inst Recerca, Hosp Santa Creu & St Pau, Barcelona, Spain
Juarez, C:
Hosp Santa Creu & Sant Pau, Dept Immunol, Barcelona, Spain
Vidal, S:
Univ Autonoma Barcelona, Dept Immunol, Inst Recerca, Hosp Santa Creu & St Pau, Barcelona, Spain
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