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IL-1α-induced microvascular endothelial cells promote neutrophil killing by increasing MMP-9 concentration and lysozyme activity

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Abstract

The recruitment of neutrophils by endothelial cells during infection has been extensively studied, but little is known about the regulation of neutrophils activity by endothelial cells. To examine the role of microvascular endothelial cells in neutrophil killing, we established a transmigration model using rat intestinal microvascular endothelial cells (RIMVECs) and measured the extracellular and intracellular killing of Escherichia coli, Lactobacillus acidophilus, and Staphylococcus aureus by transendothelial neutrophils. We observed that blood neutrophils engulfed bacteria but did not kill them, and lipopolysaccharide- or hemolysin-injured RIMVECs inhibited the extracellular and intracellular bactericidal activity of transendothelial neutrophils. In comparison, interleukin-1α-induced RIMVECs promoted the extracellular and intracellular killing activity of transendothelial neutrophils and significantly increased MMP-9 concentration and lysozyme activity in transendothelial neutrophils (p < 0.01 and p < 0.001, respectively). Our results demonstrated that activation of endothelial cells enhanced bactericidal activity of transendothelial neutrophils and bacterial toxin damage of endothelial cells led to reduction in bactericidal activity of transendothelial neutrophils. These findings offered new insight into the role of endothelial cells in the bactericidal activity of neutrophils.

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Abbreviations

MVECs:

Microvascular endothelial cells

RIMVECs:

Rat intestinal microvascular endothelial cells

LPS:

Lipopolysaccharide

HLα:

α-Hemolysin

IL-1α:

Interleukin-1 alpha

LDH:

Lactate dehydrogenase

TEER:

Transendothelial electrical resistance

MMP-9:

Matrix metalloproteinases-9

E. coli :

Escherichia coli

L. acidophilus :

Lactobacillus acidophilus

S. aureus :

Staphylococcus aureus

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Acknowledgments

This work was supported by Chinese National Science Foundation Project (31272144 and 31572558), 2011 National “Twelfth Five-Year” Plan for Science & Technology Support (2011BAD34B03), the Beijing Nova Program (Z141105001814041), Beijing Municipal Science and Technology Project (Z121100007412004), the Beijing Nova Program (Z141105001814041), Beijing Municipal Natural Science Foundation (6132007).

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Correspondence to Hong Dong or Xiang Mu.

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Liu, X., Dong, H., Wang, M. et al. IL-1α-induced microvascular endothelial cells promote neutrophil killing by increasing MMP-9 concentration and lysozyme activity. Immunol Res 64, 133–142 (2016). https://doi.org/10.1007/s12026-015-8731-4

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