Miltenyi Biotec GmbH
Originally published online as doi:10.1189/jlb.0809563 on October 30, 2009

Published online before print October 30, 2009
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(Journal of Leukocyte Biology. 2010;87:323-332.)
© 2010 Society for Leukocyte Biology

Leukotriene B4 mediates {gamma}{delta} T lymphocyte migration in response to diverse stimuli

Maria Fernanda de Souza Costa*,1, Raquel de Souza-Martins*,1, Mariana C. de Souza*, Cláudia F. Benjamim{dagger}, Bruno Piva{ddagger}, Bruno L. Diaz{ddagger}, Marc Peters-Golden§, Maria das Graças Henriques*,3, Cláudio Canetti{ddagger},2 and Carmen Penido*,2,3

* Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;
{dagger} Laboratorio de Inflamação e Câncer, Instituto de Ciencias Biomédicas, and
{ddagger} Laboratório de Inflamação, Programa de Imunologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and
§ Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA

3. Correspondence: Laboratório de Farmacologia Aplicada, Departamento de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ, CEP 21041-250, Brazil. E-mail: cpenido{at}far.fiocruz.br; gracahenriques{at}fiocruz.br

ABSTRACT

Herein, we investigated the involvement of the 5-LO-derived lipid mediator LTB4 in {gamma}{delta} T cell migration. When injected into the i.pl. space of C57BL/6 mice, LTB4 triggered {gamma}{delta} T lymphocyte mobilization in vivo, a phenomenon also observed in in vitro chemotaxis assays. The i.pl. injection of Escherichia coli endotoxin (LPS) triggered increased levels of LTB4 in pleural cavities. The in vivo inhibition of LTB4 biosynthesis by the 5-LO inhibitor zileuton or the FLAP inhibitor MK886 attenuated LPS-induced {gamma}{delta} T cell accumulation into pleural cavities. Accordingly, 5-LO KO mice failed to recruit {gamma}{delta} T cells into the inflammatory site after i.pl. LPS. Antagonists of the high-affinity LTB4 receptor BLT1, CP105,696, and LY292476 also attenuated LPS-induced {gamma}{delta} T cell accumulation in pleural cavities as well as in vitro chemotaxis toward pleural washes obtained from LPS-simulated mice. LTB4/BLT1 also accounted for {gamma}{delta} T cell migration induced by i.pl. administration of Mycobacterium bovis BCG or antigen in sensitized mice. BLT1 was expressed on naïve, resident as well as LPS-recruited {gamma}{delta} T cells. Isolated {gamma}{delta} T cells were found to undergo F-actin cytoskeleton reorganization when incubated with LTB4 in vitro, confirming that {gamma}{delta} T lymphocytes can respond directly to LTB4. In addition to its direct effect on {gamma}{delta} T cells, LTB4 triggered their accumulation indirectly, via modulation of CCL2 production in mouse pleural cavities. These data show that {gamma}{delta} T cell migration into the pleural cavity of mice during diverse inflammatory responses is dependent on LTB4/BLT1.

Key Words: inflammation • T cells • lipid mediators