Involvement of CC chemokines in gammadelta T lymphocyte trafficking during allergic inflammation: the role of CCL2/CCR2 pathway.
In the present study, we show that the intra-thoracic injection of ovalbumin (OVA, 12.5 microg per cavity) into C57BL/10 mice induced a significant increase in gammadelta T lymphocyte numbers in the pleural cavity, blood and thoracic lymph node of challenged mice. Such increase was significant within 12 h, peaked within 48 h and returned to basal counts within 120 h. Levels of CC chemokine ligand (CCL)-2/monocyte chemotactic protein-1, CCL5/regulated upon activation, normal T cell expressed and secreted, CCL3/macrophage inflammatory protein-1 alpha and CCL25/thymus-expressed chemokine were above control values in pleural washes recovered 24 h after OVA challenge (OPW) and were likely produced by pleural macrophages and mesothelial cells. Antigenic challenge also induced an up-regulation in CC chemokine receptor (CCR)-2, CCR5 and CCR9 on gammadelta T cells from pleural cavities, blood and lymph nodes, suggesting that cells found in mice pleural cavity migrate from secondary lymphoid organs into the inflammatory site via blood stream. The in vitro neutralization of CCL2 (but not of CCL3, CCL5 or CCL25) abrogated OPW-induced gammadelta T lymphocyte transmigration. Confirming such results, the in vivo administration of alpha-CCL2 mAb inhibited gammadelta T lymphocyte accumulation in the pleural cavity of challenged mice, whereas the blockade of CCL3, CCL5 or CCL25 showed no effect on gammadelta T cell mobilization. In addition, OVA challenge failed to induce gammadelta T lymphocyte accumulation in the pleural cavity of C57BL/6 CCR2 knockout mice, which also showed decreased numbers of these cells in blood and lymph nodes when compared with wild-type mice. Overall, such results demonstrate that CCR2/CCL2 pathway is crucial for gammadelta T lymphocyte mobilization during the allergic response.
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. cpenido@far.fiocruz.br
Carmen
C
Penido
Maria F S
MF
Costa
Mariana C
MC
Souza
Karina A
KA
Costa
Andre L P
AL
Candéa
Claudia F
CF
Benjamim
Maria das Graças M O
Md
Henriques
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010994:Pleura / Q000166:cytology / Q000276:immunology; D010998:Pleurisy / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054390:Receptors, CCR2; D010047:Ovalbumin