Role of monocyte chemotactic protein-1/CC chemokine ligand 2 on gamma delta T lymphocyte trafficking during inflammation induced by lipopolysaccharide or Mycobacterium bovis bacille Calmette-Guérin.
Gammadelta T lymphocytes are involved in a great variety of inflammatory and infectious responses. However, the mechanisms by which gammadelta T lymphocytes migrate to inflamed sites are poorly understood. In this study we investigate the role of monocyte chemotactic protein (MCP)-1 in regulating gammadelta T cell migration after LPS or Mycobacterium bovis bacille Calmette-Guérin (BCG) challenge. LPS-induced gammadelta T cell influx was significantly inhibited by either pretreatment with dexamethasone or vaccinia virus Lister 35-kDa chemokine binding protein, vCKBP, a CC chemokine neutralizing protein, suggesting a role for CC chemokines in this phenomenon. LPS stimulation increased the expression of MCP-1 mRNA and protein at the inflammation site within 6 h. It is noteworthy that LPS was unable to increase MCP-1 production or gammadelta T cell recruitment in C3H/HeJ, indicative of the involvement of Toll-like receptor 4. Gammadelta T cells express MCP-1 receptor CCR2. Pretreatment with anti-MCP-1 mAb drastically inhibited LPS-induced in vivo gammadelta T cell mobilization. Indeed, MCP-1 knockout mice were unable to recruit gammadelta T cells to the pleural cavity after LPS stimulation, effect that could be restored by coadministration of MCP-1. In addition, BCG-induced gammadelta lymphocyte accumulation was significantly reduced in MCP-1 knockout mice when compared with wild-type mice. In conclusion, our results indicate that LPS-induced gammadelta T lymphocyte migration is dependent on Toll-like receptor 4 and sensitive to both dexamethasone and CC chemokine-binding protein inhibition. Moreover, by using MCP-1 neutralizing Abs and genetically deficient mice we show that LPS- and BCG-induced gammadelta T lymphocyte influx to the pleural cavity of mice is mainly orchestrated by the CC chemokine MCP-1.
Penido
Carmen
C
Laboratório de Imunofarmacologia, Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil.
Vieira-de-Abreu
Adriana
A
Bozza
Marcelo T
MT
Castro-Faria-Neto
Hugo C
HC
Bozza
Patrícia T
PT
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D007442:Intubation, Intratracheal; D008024:Ligands; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology*; D010998:Pleurisy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014616:Vaccinia virus / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000494:pharmacology
D002352:Carrier Proteins; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D008024:Ligands; D008070:Lipopolysaccharides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014764:Viral Proteins