Activated endothelial cells limit inflammatory response, but increase chemoattractant potential and bacterial clearance by human monocytes

• Published in: Cell biology international Vol. 39; no. 6; pp. 721 - 732
• Main Authors: Mancilla-Herrera, Ismael, Alvarado-Moreno, José Antonio, Cérbulo-Vázquez, Arturo, Prieto-Chávez, Jessica L., Ferat-Osorio, Eduardo, López-Macías, Constantino, Estrada-Parra, Sergio, Isibasi, Armando, Arriaga-Pizano, Lourdes
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-06-2015; Wiley Subscription Services, Inc
• Subjects: bacterial clearance; Chemokines; Chemokines - metabolism; Chemotactic Factors - pharmacology; Cytokines; Extracellular Signal-Regulated MAP Kinases - metabolism; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Immune system; Inflammation; Inflammation - pathology; Leukocytes; Lipopolysaccharide Receptors - metabolism; Male; Microbial Viability - drug effects; Monocytes - drug effects; Monocytes - enzymology; Monocytes - microbiology; Monocytes - pathology; p38 Mitogen-Activated Protein Kinases - metabolism; phagocytosis; Phagocytosis - drug effects; Phosphorylation - drug effects; Toll-Like Receptor 4 - metabolism; Transendothelial and Transepithelial Migration - drug effects; transendothelial migration; phagocytosis; bacterial clearance; Inflammation; cytokines; transendothelial migration; chemokines
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.10440

Inflammation is the normal immune response of vascularized tissues to damage and bacterial products, for which leukocyte transendothelial migration (TEM) is critical. The effects of cell‐to‐cell contact seen in both leukocyte and endothelial cells include cytoskeleton rearrangement, and dynamic expression of adhesion molecules and metalloproteinases. TEM induces expression of anti‐apoptotic molecules, costimulatory molecules associated with antigen presentation, and pattern recognition receptors (PRR), such as TLR‐4, in monocytes. However, little is known about how TLR‐4 increment operates in monocytes during an inflammatory response. To understand it better, we used an in vitro model in which monocytes crossed a layer of IL‐1β stimulated Human Umbilical Vein Endothelial Cells (HUVEC). After TEM, monocytes were tested for the secretion of inflammatory cytokines and chemokines, their phenotype (CD14, CD16, TLR‐4 expression), and TLR‐4 canonical [Nuclear Factor kappa B, (NF‐κB) pathway] and non‐canonical [p38, extracellular signal‐regulated kinases (ERK) 1/2 pathway] signal transduction induced by lipopolysaccharide (LPS). Phagocytosis and bacterial clearance were also measured. There was diminished secretion of LPS‐induced inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) and higher secretion of chemokines (CXCL8/IL‐8 and CCL2/MCP‐1) in supernatant of TEM monocytes. These changes were accompanied by increases in TLR‐4, CD14 (surfaces expression), p38, and ERK1/2 phosphorylated cytoplasmic forms, without affecting NF‐κB activation. It also increased bacterial clearance after TEM by an O2‐independent mechanism. The data suggest that interaction between endothelial cells and monocytes fine‐tunes the inflammatory response and promotes bacterial elimination.