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Published online before print October 30, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0707495

Received for publication July 26, 2007.
Revised September 12, 2007.
Accepted for publication October 4, 2007.

Article

Attenuated translocation of group IVa phospholipase A2 and annexin-1 synthesis prevents glucocorticoid-induced blockade of {beta}2-integrin adhesion in neutrophils

Angelo Y. Meliton *, Nilda M. Munoz *@, Xiangdong Zhu *, and Alan R. Leff *{dagger}

*Departments of Medicine, {dagger}Pediatrics, Pharmacology and Physiology and Committees on Molecular Medicine, Clinical Pharmacology and Pharmacogenomics, and Cell Physiology, The University of Chicago, Chicago, Illinois, USA

@ To whom correspondence should be addressed. E-mail: nmunoz{at}medicine.bsd.uchicago.edu.


  Abstract

We examined the effect of glucocorticoid stimulation in blocking {beta}2-integrin adhesion of polymorphonuclear leukocytes (PMNs) isolated from normal human subjects. Surface expression of CD11b and ERK-1/2-mediated gIVaPLA2 phosphorylation, which are required for {beta}2-integrin adhesion, were not affected by treatment with ≤10-6 M fluticasone propionate (FP) for PMNs activated by either 10-7 M LTB4 or 30 ng/ml TNF-{alpha} and caused no significant blockade of {beta}2-integrin adhesion in vitro. Baseline expression of annexin-1 (ANXA1) synthesis was increased only after 10-6 M FP for PMNs; by contrast, comparable increase in ANXA1 expression was demonstrated in human eosinophils from the same subjects with 10-8 M FP. Viability of PMNs was verified by propidium iodide and by the persistence of {beta}2-integrin adhesion in treated groups. Exogenous administration of ANXA1 mimetic peptide fragment blocked significantly and comparably the {beta}2-integrin adhesion in PMNs activated by LTB4 and TNF-{alpha} and in eosinophils activated by IL-5. Translocation of gIVaPLA2 from the cytosol to the nucleus also was refractory for activated PMNs treated with ≥10-7 M FP; by contrast, complete blockade of nuclear translocation of cytosolic gIVaPLA2 was effected by 10-9 M FP in eosinophils. Our data indicate that the cell surface ANXA1 synthesis is capable of blocking {beta}2-integrin adhesion in both PMNs and eosinophils. However, in contrast to eosinophils, FP does not cause either substantial ANXA1 synthesis or nuclear transport of cytosolic gIVaPLA2 in PMNs and thus does not block {beta}2-integrin adhesion, a necessary step for granulocyte cell migration in vivo.

Key Words: fluticasone propionate • granulocytes • gIVaPLA2 • signal transduction • annexin-1 mimetic






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Copyright © 2007 by the Society for Leukocyte Biology.