Leukotriene B4 mediates γδ T lymphocyte migration in response to diverse stimuli

Journal of Leukocyte Biology

Mariana C. de Souza²  Cláudio Canetti³  Cláudia F. Benjamim¹  Maria Fernanda de Souza Costa²  Bruno L. Diaz³  Raquel de Souza-Martins²  Bruno Piva³  Marc Peters-Golden⁴  Maria das Graças Henriques²  Carmen Penido² 

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

关键词: inflammation;    T cells;    lipid mediators;   

DOI  :  10.1189/jlb.0809563

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Herein, we investigated the involvement of the 5-LO-derived lipid mediator LTB4 in γδ T cell migration. When injected into the i.pl. space of C57BL/6 mice, LTB4 triggered γδ 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 γδ T cell accumulation into pleural cavities. Accordingly, 5-LO KO mice failed to recruit γδ 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 γδ 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 γδ 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 γδ T cells. Isolated γδ T cells were found to undergo F-actin cytoskeleton reorganization when incubated with LTB4 in vitro, confirming that γδ T lymphocytes can respond directly to LTB4. In addition to its direct effect on γδ T cells, LTB4 triggered their accumulation indirectly, via modulation of CCL2 production in mouse pleural cavities. These data show that γδ T cell migration into the pleural cavity of mice during diverse inflammatory responses is dependent on LTB4/BLT1.

【 授权许可】

Unknown