Leukotriene B4 mediates gammadelta T lymphocyte migration in response to diverse stimuli.
Herein, we investigated the involvement of the 5-LO-derived lipid mediator LTB(4) in gammadelta T cell migration. When injected into the i.pl. space of C57BL/6 mice, LTB(4) triggered gammadelta 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 LTB(4) in pleural cavities. The in vivo inhibition of LTB(4) biosynthesis by the 5-LO inhibitor zileuton or the FLAP inhibitor MK886 attenuated LPS-induced gammadelta T cell accumulation into pleural cavities. Accordingly, 5-LO KO mice failed to recruit gammadelta T cells into the inflammatory site after i.pl. LPS. Antagonists of the high-affinity LTB(4) receptor BLT1, CP105,696, and LY292476 also attenuated LPS-induced gammadelta T cell accumulation in pleural cavities as well as in vitro chemotaxis toward pleural washes obtained from LPS-simulated mice. LTB(4)/BLT1 also accounted for gammadelta 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 gammadelta T cells. Isolated gammadelta T cells were found to undergo F-actin cytoskeleton reorganization when incubated with LTB(4) in vitro, confirming that gammadelta T lymphocytes can respond directly to LTB(4). In addition to its direct effect on gammadelta T cells, LTB(4) triggered their accumulation indirectly, via modulation of CCL2 production in mouse pleural cavities. These data show that gammadelta T cell migration into the pleural cavity of mice during diverse inflammatory responses is dependent on LTB(4)/BLT1.
Costa
Maria Fernanda de Souza
MF
Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, RJ, CEP 21041-250, Brazil.
de Souza-Martins
Raquel
R
de Souza
Mariana C
MC
Benjamim
Cláudia F
CF
Piva
Bruno
B
Diaz
Bruno L
BL
Peters-Golden
Marc
M
Henriques
Maria das Graças
Md
Canetti
Cláudio
C
Penido
Carmen
C
D000199:Actins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001578:Benzopyrans; D002264:Carboxylic Acids; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007975:Leukotriene B4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000199:Actins; D001578:Benzopyrans; D002264:Carboxylic Acids; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; C503704:Ltb4r1 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; C089698:CP 105696