Independent roles of macrophage migration inhibitory factor and endogenous, but not exogenous glucocorticoids in regulating leukocyte trafficking.
Microcirculation
; 16(8): 735-48, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19905972
ABSTRACT
OBJECTIVES:
Macrophage migration inhibitory factor (MIF) promotes leukocyte recruitment and antagonizes the anti-inflammatory effects of glucocorticoids (GC). The aim of this study was to examine whether interaction between MIF and GC underlies the ability of MIF to promote leukocyte-endothelial cell (EC) interactions.METHODS:
Intravital microscopy was used to assess leukocyte-EC interactions in wild-type and MIF(-/-) mice following treatment with lipopolysaccharide (LPS), the GC dexamethasone, and inhibition of endogenous GC, using the GC-receptor antagonist, RU486.RESULTS:
Dexamethasone reduced LPS-induced leukocyte interactions in wild-type mice to levels similar to those observed in MIF(-/-) mice not treated with dexamethasone, whereas in MIF(-/-) mice, leukocyte interactions were not further inhibited by dexamethasone. RU486 increased LPS-induced leukocyte adhesion and emigration to a similar extent in both wild-type and MIF(-/-) mice, indicating that endogenous GC exert a similar inhibitory effect on leukocyte trafficking in wild-type and MIF(-/-) mice. Both MIF deficiency and RU486 treatment reduced VCAM-1 expression, while neither treatment modulated expression of ICAM-1 or chemokines CCL2, KC, and MIP-2.CONCLUSIONS:
These results suggest that endogenous MIF and GC regulate leukocyte-EC interactions in vivo reciprocally but through predominantly independent mechanisms, and that the anti-inflammatory effect of MIF deficiency is comparable to that of exogenous GC.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Quimiotaxia de Leucócito
/
Fatores Inibidores da Migração de Macrófagos
/
Glucocorticoides
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article