Glucocorticoid-induced surface expression of annexin 1 blocks beta2-integrin adhesion of human eosinophils to intercellular adhesion molecule 1 surrogate protein.
BACKGROUND
Glucocorticoids attenuate the population of eosinophils and T lymphocytes in asthmatic airways. The decrease in airway eosinophilia is caused both by accelerated cell death and by induction of blockade of integrin adhesion. In this study, we examined the hypothesis that annexin 1 surface expression, which is upregulated by the glucocorticoid receptor, prevents integrin adhesion essential to cell migration by blocking intracellular translocation of cytosolic group IV phospholipase A2 (cPLA2).


OBJECTIVE
To examine the relationship of the glucocorticoid on annexin 1 expression and the effect of blockade of annexin 1 activity on adhesion of human eosinophils in vitro. To determine the relationship between annexin 1surface expression and nuclear membrane translocation of cPLA2.


METHODS
Eosinophils isolated from human peripheral blood were pretreated with fluticasone propionate (FP), and beta2-integrin adhesion was measured after stimulation with IL-5 or eotaxin. Effects of FP on cPLA2 expression, phosphorylation, and translocation were determined. The role of annexin 1 was examined by using annexin 1 blocking antibody and/or mimetic peptides.


RESULTS
Fluticasone propionate decreased stimulated eosinophil adhesion and caused 4-fold increase in annexin 1 expression on the plasma membrane. Inhibition of adhesion by FP was blocked with annexin 1 blocking antibody. Annexin 1 N-terminal mimetic peptide also blocked beta2-integrin adhesion. Translocation of cPLA2 to the nuclear membrane was significantly blocked by incubation with FP. Blockade was reversed with annexin 1 blocking antibody.


CONCLUSIONS
Blockade of beta2-integrin adhesion by glucocorticoid is regulated by annexin 1, which blocks cPLA2 translocation to nuclear membrane.
Liu
Jie
J
Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Ill 60637, USA.
Zhu
Xiangdong
X
Myo
Saori
S
Lambertino
Anissa T
AT
Xu
Chang
C
Boetticher
Evan
E
Muñoz
Nilda M
NM
Sano
Masaaki
M
Cordoba
Martha
M
Learoyd
Jonathan
J
Meliton
Angelo
A
Johnson
Malcolm
M
Leff
Alan R
AR
D000730:Androstadienes / Q000494:pharmacology; D017302:Annexins / Q000096:biosynthesis / Q000187:drug effects*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015415:Biomarkers; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects* / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D000068298:Fluticasone; D005938:Glucocorticoids / Q000494:pharmacology*; D054513:Group IV Phospholipases A2; D006801:Humans; D039641:Integrin beta Chains / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009685:Nuclear Envelope / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects / Q000276:immunology
D000730:Androstadienes; D017302:Annexins; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D005938:Glucocorticoids; D039641:Integrin beta Chains; D018799:Intercellular Adhesion Molecule-1; D000068298:Fluticasone; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2