Appearance of monocyte chemoattractant protein 1 (MCP-1) early after thermal injury: role in the subsequent development of burn-associated type 2 T-cell responses.
OBJECTIVE
To determine whether monocyte chemoattractant protein-1 (MCP-1), which initiates subsequent development of burn-associated type 2 T cells, is produced in mice early after thermal injury.


BACKGROUND
A predominance of type 2 T-cell responses is commonly observed in animals and patients with severe thermal injuries. Burn-associated type 2 T cells have been identified as the cells responsible for the increased susceptibility of thermally injured mice to infections with herpes simplex virus type 1 and Candida albicans. Recently, the necessity of MCP-1 for the generation of type 2 T cells was shown in MCP-1 knockout mice. MCP-1 may have an important role in the increased susceptibility of thermally injured mice to various intracellular opportunistic pathogens.


METHODS
The production of MCP-1 in sera or in cultures of various cells prepared from thermally injured mice was measured. Dual-chamber transwell cultures were performed to determine the influence of MCP-1-producing cells on the generation of burn-associated type 2 T cells.


RESULTS
Without any stimulation, splenic macrophages from mice (1/2D-M(phi)) produced MCP-1 into their culture fluids 12 hours after thermal injury. Interleukin-4 was detected in culture fluids of splenic T cells from normal mice cultured with 1/2D-M(phi) in a dual-chamber transwell system; however, this cytokine was not produced by normal T cells cultured with normal macrophages in the transwells. Also, normal T cells cultured with 1/2D-M(phi) did not produce interleukin-4 when transwell cultures were performed in the presence of anti-MCP-1 monoclonal antibody. Further, normal T cells directly stimulated with MCP-1 produced interleukin-4 into their culture fluids. Normal T cells, cultured with 1/2D-M(phi) for 24 hours in the transwells and recultured with fresh medium for an additional 7 days, produced interleukin-10 (but not interferon-gamma) and expressed ST2L mRNA (but not interleukin-12 receptor beta2 chain) when they were stimulated with anti-CD3 monoclonal antibody.


CONCLUSIONS
Results indicate that MCP-1 is produced in mice within 1 day of thermal injury, and the subsequent development of burn-associated type 2 T-cell responses may be triggered by MCP-1 produced early after thermal injury.
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas 77555-0435, USA.
Katsunori
K
Furukawa
Makiko
M
Kobayashi
David N
DN
Herndon
Richard B
RB
Pollard
Fujio
F
Suzuki
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002056:Burns / Q000276:immunology*; D018932:Chemokine CCL2 / Q000032:analysis* / Q000096:biosynthesis* / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D015847:Interleukin-4 / Q000032:analysis* / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015415:Biomarkers; D018932:Chemokine CCL2; D015847:Interleukin-4