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Stimulation of hematopoiesis by the Fms-like tyrosine kinase 3 ligand restores bacterial induction of Th1 cytokines in thermally injured mice.
Infect Immun. 2003 Jun; 71(6):3058-67.II

Abstract

Patients with large burn injuries are susceptible to opportunistic infections due to impaired functions of multiple effector cells of innate immunity and acquired immunity, including macrophages, dendritic cells (DC), natural killer (NK) cells, and T cells. The ability of a host to produce Th1 cytokines, such as gamma interferon (IFN-gamma) and interleukin-12 (IL-12), upon infectious challenge is also impaired after burn injury. Stimulation of hematopoiesis, to regenerate new immune cells, may be an effective strategy for improving resistance to infections after severe burn trauma. Fms-like tyrosine kinase 3 ligand (Flt3L) is a hematopoietic cytokine that stimulates the expansion and differentiation of NK cells and DC. Using a mouse model, we tested the hypothesis that Flt3L treatments after burn injury stimulate the production of functional effector cells of innate immunity and restore appropriate Th1 cytokine responses to Pseudomonas aeruginosa, a common source of pneumonia and wound infections in burn victims. Flt3L increased splenic cellularity in sham (uninjured) and burned mice and increased the numbers of NK cells (DX5(+)) and DC (CD11c(+)). In response to P. aeruginosa, significant increases in the serum IFN-gamma levels and the numbers of splenic IFN-gamma-producing DC, NK cells, and T cells were observed in Flt3L-treated burned mice compared to the values obtained for untreated burned mice. The splenic levels of IL-12 and IL-15 mRNAs and the IL-12 and IL-15 receptors were also increased. In addition, Flt3L treatment restored the ability of splenic cultures prepared from burned mice to produce IFN-gamma and IL-12 after in vitro challenge with P. aeruginosa. Flt3L may have potential for restoring NK cell and DC functions and improving immunity after burn injury.

Authors+Show Affiliations

Department of Anesthesiology, The University of Texas Medical Branch, Galveston 77555, USA. ttoliver@utmb.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12761083

Citation

Toliver-Kinsky, Tracy E., et al. "Stimulation of Hematopoiesis By the Fms-like Tyrosine Kinase 3 Ligand Restores Bacterial Induction of Th1 Cytokines in Thermally Injured Mice." Infection and Immunity, vol. 71, no. 6, 2003, pp. 3058-67.
Toliver-Kinsky TE, Lin CY, Herndon DN, et al. Stimulation of hematopoiesis by the Fms-like tyrosine kinase 3 ligand restores bacterial induction of Th1 cytokines in thermally injured mice. Infect Immun. 2003;71(6):3058-67.
Toliver-Kinsky, T. E., Lin, C. Y., Herndon, D. N., & Sherwood, E. R. (2003). Stimulation of hematopoiesis by the Fms-like tyrosine kinase 3 ligand restores bacterial induction of Th1 cytokines in thermally injured mice. Infection and Immunity, 71(6), 3058-67.
Toliver-Kinsky TE, et al. Stimulation of Hematopoiesis By the Fms-like Tyrosine Kinase 3 Ligand Restores Bacterial Induction of Th1 Cytokines in Thermally Injured Mice. Infect Immun. 2003;71(6):3058-67. PubMed PMID: 12761083.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stimulation of hematopoiesis by the Fms-like tyrosine kinase 3 ligand restores bacterial induction of Th1 cytokines in thermally injured mice. AU - Toliver-Kinsky,Tracy E, AU - Lin,Cheng Y, AU - Herndon,David N, AU - Sherwood,Edward R, PY - 2003/5/23/pubmed PY - 2003/6/20/medline PY - 2003/5/23/entrez SP - 3058 EP - 67 JF - Infection and immunity JO - Infect. Immun. VL - 71 IS - 6 N2 - Patients with large burn injuries are susceptible to opportunistic infections due to impaired functions of multiple effector cells of innate immunity and acquired immunity, including macrophages, dendritic cells (DC), natural killer (NK) cells, and T cells. The ability of a host to produce Th1 cytokines, such as gamma interferon (IFN-gamma) and interleukin-12 (IL-12), upon infectious challenge is also impaired after burn injury. Stimulation of hematopoiesis, to regenerate new immune cells, may be an effective strategy for improving resistance to infections after severe burn trauma. Fms-like tyrosine kinase 3 ligand (Flt3L) is a hematopoietic cytokine that stimulates the expansion and differentiation of NK cells and DC. Using a mouse model, we tested the hypothesis that Flt3L treatments after burn injury stimulate the production of functional effector cells of innate immunity and restore appropriate Th1 cytokine responses to Pseudomonas aeruginosa, a common source of pneumonia and wound infections in burn victims. Flt3L increased splenic cellularity in sham (uninjured) and burned mice and increased the numbers of NK cells (DX5(+)) and DC (CD11c(+)). In response to P. aeruginosa, significant increases in the serum IFN-gamma levels and the numbers of splenic IFN-gamma-producing DC, NK cells, and T cells were observed in Flt3L-treated burned mice compared to the values obtained for untreated burned mice. The splenic levels of IL-12 and IL-15 mRNAs and the IL-12 and IL-15 receptors were also increased. In addition, Flt3L treatment restored the ability of splenic cultures prepared from burned mice to produce IFN-gamma and IL-12 after in vitro challenge with P. aeruginosa. Flt3L may have potential for restoring NK cell and DC functions and improving immunity after burn injury. SN - 0019-9567 UR - https://www.unboundmedicine.com/medline/citation/12761083/Stimulation_of_hematopoiesis_by_the_Fms_like_tyrosine_kinase_3_ligand_restores_bacterial_induction_of_Th1_cytokines_in_thermally_injured_mice_ L2 - http://iai.asm.org/cgi/pmidlookup?view=long&pmid=12761083 DB - PRIME DP - Unbound Medicine ER -