Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules

Qiang Cheng, Sonja Jane McKeown, Leilani Llanes Santos, Fernando S Santiago, Levon M Kachigian, Eric Francis Morand, Michael John Hickey

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Macrophage migration inhibitory factor (MIF) has been shown to promote leukocyte-endothelial cell interactions, although whether this occurs via an effect on endothelial cell function remains unclear. Therefore, the aims of this study were to examine the ability of MIF expressed by endothelial cells to promote leukocyte adhesion and to investigate the effect of exogenous MIF on leukocyte-endothelial interactions. Using small interfering RNA to inhibit HUVEC MIF production, we found that MIF deficiency reduced the ability of TNF-stimulated HUVECs to support leukocyte rolling and adhesion under flow conditions. These reductions were associated with decreased expression of E-selectin, ICAM-1, VCAM-1, IL-8, and MCP-1. Inhibition of p38 MAPK had a similar effect on adhesion molecule expression, and p38 MAPK activation was reduced in MIF-deficient HUVECs, suggesting that MIF mediated these effects via promotion of p38 MAPK activation. In experiments examining the effect of exogenous MIF, application of MIF to resting HUVECs failed to induce leukocyte rolling and adhesion, whereas addition of MIF to TNF-treated HUVECs increased these interactions. This increase was independent of alterations in TNF-induced expression of E-selectin, VCAM-1, and ICAM-1. However, combined treatment with MIF and TNF induced de novo expression of P-selectin, which contributed to leukocyte rolling. In summary, these experiments reveal that endothelial cell-expressed MIF and exogenous MIF promote endothelial adhesive function via different pathways. Endogenous MIF promotes leukocyte recruitment via effects on endothelial expression of several adhesion molecules and chemokines, whereas exogenous MIF facilitates leukocyte recruitment induced by TNF by promoting endothelial P-selectin expression.
Original languageEnglish
Pages (from-to)1238 - 1247
Number of pages10
JournalJournal of Immunology
Volume185
Issue number2
DOIs
Publication statusPublished - 2010

Cite this

@article{1a4af22cd0a34327963ae3b5c9f2d9e8,
title = "Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules",
abstract = "Macrophage migration inhibitory factor (MIF) has been shown to promote leukocyte-endothelial cell interactions, although whether this occurs via an effect on endothelial cell function remains unclear. Therefore, the aims of this study were to examine the ability of MIF expressed by endothelial cells to promote leukocyte adhesion and to investigate the effect of exogenous MIF on leukocyte-endothelial interactions. Using small interfering RNA to inhibit HUVEC MIF production, we found that MIF deficiency reduced the ability of TNF-stimulated HUVECs to support leukocyte rolling and adhesion under flow conditions. These reductions were associated with decreased expression of E-selectin, ICAM-1, VCAM-1, IL-8, and MCP-1. Inhibition of p38 MAPK had a similar effect on adhesion molecule expression, and p38 MAPK activation was reduced in MIF-deficient HUVECs, suggesting that MIF mediated these effects via promotion of p38 MAPK activation. In experiments examining the effect of exogenous MIF, application of MIF to resting HUVECs failed to induce leukocyte rolling and adhesion, whereas addition of MIF to TNF-treated HUVECs increased these interactions. This increase was independent of alterations in TNF-induced expression of E-selectin, VCAM-1, and ICAM-1. However, combined treatment with MIF and TNF induced de novo expression of P-selectin, which contributed to leukocyte rolling. In summary, these experiments reveal that endothelial cell-expressed MIF and exogenous MIF promote endothelial adhesive function via different pathways. Endogenous MIF promotes leukocyte recruitment via effects on endothelial expression of several adhesion molecules and chemokines, whereas exogenous MIF facilitates leukocyte recruitment induced by TNF by promoting endothelial P-selectin expression.",
author = "Qiang Cheng and McKeown, {Sonja Jane} and Santos, {Leilani Llanes} and Santiago, {Fernando S} and Kachigian, {Levon M} and Morand, {Eric Francis} and Hickey, {Michael John}",
year = "2010",
doi = "10.4049/jimmunol.0904104",
language = "English",
volume = "185",
pages = "1238 -- 1247",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules. / Cheng, Qiang; McKeown, Sonja Jane; Santos, Leilani Llanes; Santiago, Fernando S; Kachigian, Levon M; Morand, Eric Francis; Hickey, Michael John.

In: Journal of Immunology, Vol. 185, No. 2, 2010, p. 1238 - 1247.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules

AU - Cheng, Qiang

AU - McKeown, Sonja Jane

AU - Santos, Leilani Llanes

AU - Santiago, Fernando S

AU - Kachigian, Levon M

AU - Morand, Eric Francis

AU - Hickey, Michael John

PY - 2010

Y1 - 2010

N2 - Macrophage migration inhibitory factor (MIF) has been shown to promote leukocyte-endothelial cell interactions, although whether this occurs via an effect on endothelial cell function remains unclear. Therefore, the aims of this study were to examine the ability of MIF expressed by endothelial cells to promote leukocyte adhesion and to investigate the effect of exogenous MIF on leukocyte-endothelial interactions. Using small interfering RNA to inhibit HUVEC MIF production, we found that MIF deficiency reduced the ability of TNF-stimulated HUVECs to support leukocyte rolling and adhesion under flow conditions. These reductions were associated with decreased expression of E-selectin, ICAM-1, VCAM-1, IL-8, and MCP-1. Inhibition of p38 MAPK had a similar effect on adhesion molecule expression, and p38 MAPK activation was reduced in MIF-deficient HUVECs, suggesting that MIF mediated these effects via promotion of p38 MAPK activation. In experiments examining the effect of exogenous MIF, application of MIF to resting HUVECs failed to induce leukocyte rolling and adhesion, whereas addition of MIF to TNF-treated HUVECs increased these interactions. This increase was independent of alterations in TNF-induced expression of E-selectin, VCAM-1, and ICAM-1. However, combined treatment with MIF and TNF induced de novo expression of P-selectin, which contributed to leukocyte rolling. In summary, these experiments reveal that endothelial cell-expressed MIF and exogenous MIF promote endothelial adhesive function via different pathways. Endogenous MIF promotes leukocyte recruitment via effects on endothelial expression of several adhesion molecules and chemokines, whereas exogenous MIF facilitates leukocyte recruitment induced by TNF by promoting endothelial P-selectin expression.

AB - Macrophage migration inhibitory factor (MIF) has been shown to promote leukocyte-endothelial cell interactions, although whether this occurs via an effect on endothelial cell function remains unclear. Therefore, the aims of this study were to examine the ability of MIF expressed by endothelial cells to promote leukocyte adhesion and to investigate the effect of exogenous MIF on leukocyte-endothelial interactions. Using small interfering RNA to inhibit HUVEC MIF production, we found that MIF deficiency reduced the ability of TNF-stimulated HUVECs to support leukocyte rolling and adhesion under flow conditions. These reductions were associated with decreased expression of E-selectin, ICAM-1, VCAM-1, IL-8, and MCP-1. Inhibition of p38 MAPK had a similar effect on adhesion molecule expression, and p38 MAPK activation was reduced in MIF-deficient HUVECs, suggesting that MIF mediated these effects via promotion of p38 MAPK activation. In experiments examining the effect of exogenous MIF, application of MIF to resting HUVECs failed to induce leukocyte rolling and adhesion, whereas addition of MIF to TNF-treated HUVECs increased these interactions. This increase was independent of alterations in TNF-induced expression of E-selectin, VCAM-1, and ICAM-1. However, combined treatment with MIF and TNF induced de novo expression of P-selectin, which contributed to leukocyte rolling. In summary, these experiments reveal that endothelial cell-expressed MIF and exogenous MIF promote endothelial adhesive function via different pathways. Endogenous MIF promotes leukocyte recruitment via effects on endothelial expression of several adhesion molecules and chemokines, whereas exogenous MIF facilitates leukocyte recruitment induced by TNF by promoting endothelial P-selectin expression.

UR - http://www.jimmunol.org/cgi/reprint/185/2/1238

U2 - 10.4049/jimmunol.0904104

DO - 10.4049/jimmunol.0904104

M3 - Article

VL - 185

SP - 1238

EP - 1247

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -