International Immunology Advance Access originally published online on December 4, 2007
International Immunology 2008 20(1):129-139; doi:10.1093/intimm/dxm128
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Involvement of CC chemokines in 
T lymphocyte trafficking during allergic inflammation: the role of CCL2/CCR2 pathway
1 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
2 Laboratório de Farmacologia da Inflamação e Resposta Celular, Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Correspondence to: C. Penido; E-mail: cpenido{at}far.fiocruz.br
In the present study, we show that the intra-thoracic injection of ovalbumin (OVA, 12.5 µg per cavity) into C57BL/10 mice induced a significant increase in 
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
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 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 T lymphocyte transmigration. Confirming such results, the in vivo administration of -CCL2 mAb inhibited T lymphocyte accumulation in the pleural cavity of challenged mice, whereas the blockade of CCL3, CCL5 or CCL25 showed no effect on T cell mobilization. In addition, OVA challenge failed to induce 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 T lymphocyte mobilization during the allergic response.
Keywords: allergic pleurisy, cell migration, chemokine receptor, T cells
Transmitting editor: S. H. E. Kaufmann
Received 27 October 2006, accepted 23 October 2007.