Injury-Induced GR-1+ Macrophage Expansion and Activation Occurs Independent of CD4 T Cell Influence

• Published in: Shock (Augusta, Ga.) Ga.), 2011-08, Vol.36 (2), p.162-169
• Main Authors: O’Leary, Fionnuala M., Tajima, Goro, Delisle, Adam J., Ikeda, Kimiko, Dolan, Sinead M., Hanschen, Marc, Mannick, John A., Lederer, James A.
• Format: Article
• Language: English
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/SHK.0b013e31821af669

Burn injury initiates an enhanced inflammatory condition referred to as the systemic inflammatory response syndrome (SIRS) or the two-hit response phenotype. Prior reports indicated that macrophages respond to injury and demonstrate a heightened reactivity to Toll-like receptor (TLR) 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 TNFα expression in GR-1+, but not GR-1− macrophages following 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 TNFα expression was not significantly different between wild-type (WT) and CD4 T cell deficient (CD4−/−) mice. However, further investigations showed that LPS-induced TNFα 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 TNFα production. These data suggest that modulating GR-1+ macrophage activation as well as CD4 T cell responses following severe injury may help control the development of SIRS and the two-hit response phenotype.