title: Injury-induced GR-1+ macrophage expansion and activation occurs independently of CD4 T-cell influence.
abstract: Burn injury initiates an enhanced inflammatory condition referred to as the systemic inflammatory response syndrome or the two-hit response phenotype. Prior reports indicated that macrophages respond to injury and demonstrate a heightened reactivity to Toll-like receptor stimulation. Since we and others observed a significant increase in splenic GR-1 F4/80 CD11b macrophages in burn-injured mice, we wished to test if these macrophages might be the primary macrophage subset that shows heightened LPS reactivity. We report here that burn injury promoted higher level TNF-α expression in GR-1, but not GR-1 macrophages, after LPS activation both in vivo and ex vivo. We next tested whether CD4 T cells, which are known to suppress injury-induced inflammatory responses, might control the activation and expansion of GR-1 macrophages. Interestingly, we found that GR-1 macrophage expansion and LPS-induced TNF-α expression were not significantly different between wild-type and CD4 T cell-deficient CD4(-/-) mice. However, further investigations showed that LPS-induced TNF-α production was significantly influenced by CD4 T cells. Taken together, these data indicate that GR-1 F4/80 CD11b macrophages represent the primary macrophage subset that expands in response to burn injury and that CD4 T cells do not influence the GR-1 macrophage expansion process, but do suppress LPS-induced TNF-α production. These data suggest that modulating GR-1 macrophage activation as well as CD4 T cell responses after severe injury may help control the development of systemic inflammatory response syndrome and the two-hit response phenotype.
authors: Department of Surgery (Immunology), Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02115, USA.
authors: Fionnuala M
authors: FM
authors: O'Leary
authors: Goro
authors: G
authors: Tajima
authors: Adam J
authors: AJ
authors: Delisle
authors: Kimiko
authors: K
authors: Ikeda
authors: Sinead M
authors: SM
authors: Dolan
authors: Marc
authors: M
authors: Hanschen
authors: John A
authors: JA
authors: Mannick
authors: James A
authors: JA
authors: Lederer
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology* / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C551746:granulocyte receptor 1, mouse