Abstract
In our previous studies, peripheral blood lineage−CD34+CD31+ cells (CD31+ IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγnull mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31+ IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31+ IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31+ IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31+ IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.
Highlights
Pseudomonas aeruginosa burn wound infection frequently develops into sepsis in severely burned patients [1,2,3]
In our accompanying paper [10], lineage2CD34+CD31+ cells (CD31+ IMC) that appeared in peripheral blood of severely burned patients have been shown to be responsible for inhibiting HBD-1 production by normal human epidermal keratinocytes (NHEK)
These results indicate that host antibacterial resistance of chimeras created with NHEK against P. aeruginosa i.d. infection is completely inhibited by experimentally induced CD31+ IMC
Summary
Pseudomonas aeruginosa burn wound infection frequently develops into sepsis in severely burned patients [1,2,3]. As an initial effector of host antibacterial innate immunities, antimicrobial peptides distributed in skin tissues contribute to control surface (wound) infections [4,5,6,7]. In our accompanying paper [10], lineage2CD34+CD31+ cells (designated as CD31+ IMC) isolated from peripheral blood of severely burned patients (patient CD31+ IMC) were shown to be inhibitory on the HBD production by normal human epidermal keratinocytes (NHEK). Lineage2CD34+ cells isolated from healthy donor peripheral blood were shown to be non-inhibitory on the peptide production by NHEK, and these cells were characterized as lineage2CD34+CD312 cells. CCL2 and IL-10 released from patient CD31+ IMC were identified as inhibitory factors for the HBD production by NHEK
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