Primed polymorphonuclear leukocytes from hemodialysis patients enhance monocyte transendothelial migration

Abstract

Increased counts and priming of peripheral polymorphonuclear leukocytes (PMNLs) are associated with future or ongoing atherosclerosis; however, the role of PMNLs in enhancing monocyte transendothelial migration is still unclear. Our aims were to examine endothelial and monocyte activation, transmigration, and posttransmigration activation induced ex vivo by in vivo primed PMNLs and the effect of antioxidants on the activation. A unique ex vivo coculture system of three cell types was developed in this study, enabling interactions among the following: primary human umbilical vein endothelial cells (HUVECs), monocytes (THP-1 cell line), and in vivo primed PMNLs from hemodialysis (HD) patients and healthy control (HC) subjects. The interactions among these cells were examined, and an intervention with superoxide dismutase and catalase was performed. Preexposed HUVECs to HD/HC PMNLs showed a significant monocyte transmigration yield, 120-170% above HCs. Monocyte exposure to HD PMNLs induced pre- and posttransmigration activation. When the three cell types were cocultivated at the same time, monocyte chemoattractant protein-1 protein levels released from HUVECs, and activation markers on HUVECs [CD54 and chemokine (C-X3-C motif) ligand 1] and monocytes [chemokine (C-X3-C) receptor 1 and chemokine (C-C motif) receptor 2] were increased. Monocyte transmigration yield decreased to 70% (compared with HC subjects) due to adherence and accumulation of monocytes to HUVECs. When superoxide dismutase and catalase were used, reduced HUVEC and monocyte activation markers brought the transmigration yields to control levels and abolished accumulation of monocytes, emphasizing the role of superoxide in this process. We conclude that peripheral primed PMNLs play a pivotal role in enhancing monocyte transendotelial migration, the hallmark of the atherosclerotic process. Primed PMNLs can be used as a mediator and a biomarker of atherosclerosis even before plaque formation. Primed polymorphonuclear leukocytes are key mediators in monocyte transendothelial migration, a new understanding of the initiation of endothelial dysfunction and monocyte activation, transmigration, and accumulation in the subendothelial layer.

Monocytes in Uremia

“…Monocytes from renal failure patients differentiate into highly activated, inflammatory and cytokine producing foam cells in vitro [139]. Monocytes are also more prone to adhere to endothelium and to transmigrate in chamber experiments [140]. These findings are closely associated with ACE expression on this cell type [45].…”

The Regulation of Neutrophil Migration in Patients with Sepsis: The Complexity of the Molecular Mechanisms and Their Modulation in Sepsis and the Heterogeneity of Sepsis Patients

“…Neutrophils can be primed before (i.e., in the circulation), during, or following transmigration, and priming mechanisms that facilitate neutrophil migration involve endothelial cells, extravascular stromal cells, extracellular matrix proteins [ 110 , 111 , 112 , 113 ], platelets [ 110 , 111 ], and other immunocompetent cells [ 112 ]. Furthermore, the priming agents include the soluble mediators C3a and C5a complement components, interferon γ, CXCL8, and tumor necrosis factor (TNF) α together with pathogen-derived agents such as formylated peptides, peptidoglycan, and Staphylococcus aureus toxins [ 107 , 108 , 109 , 114 ].…”

“…Targeting of lipid mediators. Targeting of lipids is suggested both by the importance of neutrophil membrane stiffness/lipid profile, neutrophil polarization, lipid rafts, and caveola as well as chemotactic lipid mediators in the regulation of neutrophil migration, and lipids are also important for the endothelial cell stiffness that influence neutrophil transmigration ( Section 2.3 and Section 7 ; [ 25 , 26 , 27 , 46 , 47 , 88 , 89 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 148 , 149 , 150 , 151 , 152 , 153 ]). Statins were tried in the treatment of sepsis, especially in patients with septic pulmonary infections [ 369 , 432 , 433 ].…”