Increased norepinephrine production associated with burn injuries results in CCL2 production and type 2 T cell generation.
The susceptibility of thermally injured mice (TI-mice) to various infections is markedly influenced by burn-associated type 2 T cell responses, which are common with severe thermal injuries. Previously, we have reported that CC chemokine ligand 2/monocyte chemoattractant protein-I (CCL2) is produced in mice within 1 day of thermal injury, and the subsequent development of burn-associated type 2 T cell responses are triggered by this chemokine produced early after thermal injury. In this study, influence of norepinephrine (NE) on CCL2 production in mice early after thermal injury (TI) was investigated. Peripheral blood mononuclear cells (PBMC) and peritoneal macrophages (PMphi) from TI-mice produced CCL2, but the same cell preparations from normal mice did not. This chemokine was not produced by PBMC and PMphi from TI-mice previously treated with 6-hydroxydopamine (6-OHDA), which destroys sympathetic nerve termini. NE production was increased in circulation of TI-mice, and treatment of TI-mice with 6-OHDA resulted in the inhibition of NE secretion. When PBMC from normal mice were treated with NE, they acquired the ability to produce CCL2. Splenic T cells from TI-mice produced IL-4 into their culture fluids, while the cytokine was not produced by splenic T cells from TI-mice previously treated with 6-OHDA. These results indicate that NE may have an important role on early CCL2 production and the subsequent development of burn-associated type 2 T cell responses.
Takahashi
Hitoshi
H
Department of Internal Medicine, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0435, USA.
Tsuda
Yasuhiro
Y
Kobayashi
Makiko
M
Herndon
David N
DN
Suzuki
Fujio
F
D000818:Animals; D002056:Burns / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D007111:Immunity, Cellular / Q000187:drug effects; D015847:Interleukin-4 / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009638:Norepinephrine / Q000096:biosynthesis* / Q000276:immunology; D016627:Oxidopamine / Q000494:pharmacology; D014176:Protein Biosynthesis; D013154:Spleen / Q000276:immunology; D013565:Sympatholytics / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D013565:Sympatholytics; D015847:Interleukin-4; D016627:Oxidopamine; D009638:Norepinephrine