Enhancement of Dendritic Cell Production by Fms-Like Tyrosine Kinase-3 Ligand Increases the Resistance of Mice to a Burn Wound Infection

Toliver‐Kinsky, Tracy; Cui, Weihua; Murphey, E. D.; Lin, Chin Yo; Sherwood, Edward R.

doi:10.4049/jimmunol.174.1.404

Cited by 80 publications

(83 citation statements)

References 54 publications

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“…DCs are not only affected/killed by the systemic inflammatory response but may also contribute to the development of immune suppression during sepsis by impaired functions such as reduced IL-12 production or decreased capacity to activate T cells (74). Accordingly, in several murine studies, secondary infections and mortality have been reversed by administration of DCs purified from naive animals (75) or fms-like tyrosine kinase 3 ligand (FLT3-L, a DC growth factor) (76,77).…”

Section: Antigen-presenting Cells: Dendritic Cellsmentioning

confidence: 99%

“…Given the central role of DCs in both innate and adaptive immune responses, increasing their number and restoring their function might constitute another potential treatment. In particular, the use of FLT3-L-known to activate and expand DCs-was shown to reverse immunoparalysis in a mouse model of endotoxin tolerance (77) and to increase resistance to P. aeruginosa opportunistic infections in burned mice (76). In human patients, phase II/III trials have been conducted in cancer patients, but not yet in sepsis.…”

Section: Future Therapeutic Strategies and Conclusionmentioning

confidence: 99%

See 1 more Smart Citation

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

Monneret

Venet

Pachot

et al. 2008

Mol Med

302

323

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Section: Antigen-presenting Cells: Dendritic Cellsmentioning

confidence: 99%

Section: Future Therapeutic Strategies and Conclusionmentioning

confidence: 99%

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

Monneret

Venet

Pachot

et al. 2008

Mol Med

302

323

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“…We previously reported that resistance to burn wound infection, in terms of survival, could be conferred to recipient mice by the adoptive transfer of isolated DC from Flt3L-treated, but not control-treated, donor mice (28), indicating that the protective effects of Flt3L are mediated by DC. Although expression of the Flt3 receptor is decreased during DC development, differentiated DC maintain a low level of Flt3 receptor expression, suggesting that Flt3L may have some direct effects on differentiated DC in addition to their hemopoietic precursors (16,64).…”

Section: Figurementioning

confidence: 99%

“…Resistance could be conferred by DC from Flt3L-treated mice (28), leading to the hypothesis that Flt3L indirectly increases resistance to infection by enhancing DC interactions with, and activation of, other effector cells of the immune response. This study was designed to test the hypothesis that expansion or functional enhancement of DC by Flt3L treatments leads to enhancement of global immune responses upon infection.…”

mentioning

confidence: 99%

Prophylactic Treatment with Fms-Like Tyrosine Kinase-3 Ligand after Burn Injury Enhances Global Immune Responses to Infection

Bohannon

Cui²,

Cox

et al. 2008

The Journal of Immunology

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Severely burned patients are susceptible to infections with opportunistic organisms due to altered immune responses and frequent wound contamination. Immunomodulation to enhance systemic and local responses to wound infections may be protective after burn injury. We previously demonstrated that pretreatments with fms-like tyrosine kinase-3 (Flt3) ligand (Flt3L), a dendritic cell growth factor, increase the resistance of mice to a subsequent burn injury and wound infection by a dendritic cell-dependent mechanism. This study was designed to test the hypothesis that Flt3L administration after burn injury decreases susceptibility to wound infections by enhancing global immune cell activation. Mice were treated with Flt3L after burn injury and examined for survival, wound and systemic bacterial clearance, and immune cell activation after wound inoculation with Pseudomonas aeruginosa. To gain insight into the local effects of Flt3L at the burn wound, localization of Langerhans cells was examined. Mice treated with Flt3L had significantly greater numbers of CD25-expressing T cells and CD69-expressing T and B cells, neutrophils, and macrophages after, but not before, infection. Overall leukocyte apoptosis in response to infection was decreased with Flt3L treatment. Survival and local and systemic bacterial clearance were enhanced by Flt3L. Langerhans cells appeared in the dermis of skin bordering the burn wound, and further increased in response to wound infection. Flt3L augmented the appearance of Langerhans cells in response to both injury and infection. These data suggest that dendritic cell enhancement by Flt3L treatments after burn injury protects against opportunistic infections through promotion of local and systemic immune responses to infection.

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“…It has been reported that human skin keratinocytes and fibroblasts express Flt3-L [41]. Studies on the infection of burns in a mouse model showed that treatment with Flt3-L could lead to an enhancement of the dendritic cell number and functions, which in turn could stimulate neutrophil recruitment and function in the immune response to the infection [42][43][44]. IL-6 is mainly secreted by epidermal keratinocytes, while macrophages, Langerhans cells and fibroblasts in the dermis are the other sources in the skin [45,46].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of wound closure in diabetic mice by ex vivo expanded cord blood CD34+ cells

Chotinantakul¹,

Dechsukhum²,

Dejjuy³

et al. 2013

Cellular and Molecular Biology Letters

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Diabetes can impair wound closure, which can give rise to major clinical problems. Most treatments for wound repair in diabetes remain ineffective. This study aimed to investigate the influence on wound closure of treatments using expanded human cord blood CD34 + cells (CB-CD34 + cells), freshly isolated CB-CD34 + cells and a cytokine cocktail. The test subjects were mice with streptozotocin-induced diabetes. Wounds treated with fresh CB-CD34 + cells showed more rapid repair than mice given the PBS control. Injection of expanded CB-CD34 + cells improved wound closure significantly, whereas the injection of the cytokine cocktail alone did not improve wound repair. The results also demonstrated a significant decrease in epithelial gaps and advanced re-epithelialization over the wound bed area after treatment with either expanded CB-CD34 + cells or freshly isolated cells compared with the control. In addition, treatments with both CB-CD34 + cells and the cytokine cocktail were shown to promote recruitment of CD31 + -endothelial cells in the wounds. Both the CB-CD34 + cell population and the cytokine treatments also enhanced the recruitment of CD68-positive cells in the early stages (day 3) of treatment compared with PBS control, although the degree of this enhancement was found to decline in the later stages (day 9). These results demonstrated that expanded CB-CD34 + cells or freshly isolated CB-CD34 + cells could accelerate wound repair by increasing the recruitment of macrophages and capillaries and the reepithelialization over the wound bed area. Our data suggest an effective role in wound closure for both ex vivo expanded CB-CD34 + cells and freshly isolated cells, and these may serve as therapeutic options for wound treatment for diabetic patients. Wound closure acceleration by expanded CB-CD34 + cells also breaks the insufficient quantity obstacle of stem cells per unit of cord blood and other stem cell sources, which indicates a broader potential for autologous transplantation.

show abstract

Enhancement of Dendritic Cell Production by Fms-Like Tyrosine Kinase-3 Ligand Increases the Resistance of Mice to a Burn Wound Infection

Cited by 80 publications

References 54 publications

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

Prophylactic Treatment with Fms-Like Tyrosine Kinase-3 Ligand after Burn Injury Enhances Global Immune Responses to Infection

Enhancement of wound closure in diabetic mice by ex vivo expanded cord blood CD34+ cells

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