Contribution of the sympathetic nervous system on the burn-associated impairment of CCL3 production.
Previously, we have reported that the susceptibility of burned patients to infectious complications is increased when the production of CC-chemokine ligand 3 (CCL3) is impaired. In this study, the role of the sympathetic nervous system on impaired CCL3 production and antibacterial resistance following burn injuries was investigated. Normal mice were resistant (65% survival) to cecal ligation and puncture (CLP)-induced sepsis, while the same CLP killed 90% of thermally injured mice (TI-mice). However, TI-mice resisted CLP-induced sepsis (60% survival) when they were previously treated with CCL3 or sympathectomized with 6-hydroxydopamine (6-OHDA). Augmentation of host resistance against CLP-induced sepsis by 6-OHDA was abrogated by anti-CCL3 mAb treatment. Norepinephrine (NE) production was increased in circulation of TI-mice, and treatment of TI-mice with 6-OHDA resulted in the inhibition of NE secretion. CCL3 production was impaired in cultures of T cells from TI-mice or normal T cells treated with NE, even when stimulated with anti-CD3 mAb. However, CCL3 was produced by mAb-stimulated T cells from TI-mice previously treated with 6-OHDA. These results indicated that by inhibiting CCL3 production the sympathetic nervous system contributes to the increased susceptibility of TI-mice to sepsis.
Takahashi
Hitoshi
H
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555-0435, USA.
Kobayashi
Makiko
M
Tsuda
Yasuhiro
Y
Herndon
David N
DN
Suzuki
Fujio
F
D000818:Animals; D002056:Burns / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009638:Norepinephrine / Q000097:blood / Q000172:deficiency; D016627:Oxidopamine / Q000494:pharmacology; D018805:Sepsis / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D016627:Oxidopamine; D009638:Norepinephrine