Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation

Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation

Author Gastardelo, Thais Santana Autor UNIFESP Google Scholar
Damazo, Amilcar Sabino Autor UNIFESP Google Scholar
Dalli, Jesmond Google Scholar
Flower, Roderick J. Google Scholar
Perretti, Mauro Google Scholar
Oliani, Sonia Maria Autor UNIFESP Google Scholar
Institution São Paulo State Univ
Universidade Federal de São Paulo (UNIFESP)
Queen Mary Univ London
Abstract The purpose of this study was twofold: to reveal cellular events associated with the protective role of endogenous annexin A1 (AnxA1) in inflammation and to highlight the potential involvement of members of the formyl peptide receptor (Fpr) family in this process. We found that wild-type, AnxA1-null, and Fpr1-null mice all displayed an intense neutrophil recruitment into the peritoneal cavity as assessed 4 hours after carrageenin injection, and that this recruitment was most pronounced in AnxA1-null mice. in addition, this cell influx could be inhibited by the AnxA1 pharmacophore peptide, Ac2-26, in wild-type, AnxA1-null, and Fpr1-null mice, but was restored when co-treated with the pan-receptor antagonist Boc2. Using the LacZ gene reporter assay, an enhancement of AnxA1 gene promoter activity in extravasated neutrophils was evident in AnxA1-null mice; again this response was reduced after peptide treatment. the lack of functional involvement of Fpr1 prompted us to monitor the structurally related receptor Fpr2. We report, for the first time, the ultrastructural immunocytochemical co-localization of Fpr2 with AnxA1 in neutrophils that migrate into the mesenteric microcirculation and extravasate into the peritoneal fluid. Collectively, these data provide in vivo support to the hypothesis that endogenous AnxA1 is an essential effector of endogenous anti-inflammation and provide an ultrastructural indication that this mediator interacts with Fpr2 in murine neutrophils. We believe that these findings could significantly affect the development of novel therapeutics, which are modeled after the anti-migratory actions of AnxA1. (Am J Pathol 2009, 174:177-183; DOI. 10.2353/ajpath.2009.080342)
Language English
Sponsor Fundacao de Amparo 6 Pesquisa do Estado de São Paulo
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Wellcome Trust
William Harvey Research Foundation
Grant number Fundacao de Amparo 6 Pesquisa do Estado de São Paulo: 03/11292-0
Fundacao de Amparo 6 Pesquisa do Estado de São Paulo: 04/03124-3
CNPq: 307920/2004-6
Wellcome Trust: 069234/Z/02/Z
Date 2009-01-01
Published in American Journal of Pathology. Bethesda: Amer Soc Investigative Pathology, Inc, v. 174, n. 1, p. 177-183, 2009.
ISSN 0002-9440 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Investigative Pathology, Inc
Extent 177-183
Origin http://dx.doi.org/10.2353/ajpath.2009.080342
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000262219400018
URI http://repositorio.unifesp.br/handle/11600/31135

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