Lineage-CD34+CD31+ Cells That Appear in Association with Severe Burn Injury Are Inhibitory on the Production of Antimicrobial Peptides by Epidermal Keratinocytes

Antimicrobial peptides are major host defense effectors against Pseudomonas aeruginosa skin infections. Due to the lack of such peptide production, severely burned hosts are greatly susceptible to P. aeruginosa burn wound infection. beta-Defensin (HBD) production by normal human epidermal keratinocytes (NHEK) was inhibited by lineage(-)CD34(+) cells isolated from peripheral blood of severely burned patients. Lineage(-)CD34(+) cells obtained from severely burned patients were characterized as CD31(+), while healthy donor lineage(-)CD34(+) cells were shown to be CD31 2 cells. Lineage(-)CD34(+)CD31(-) cells did not show any inhibitory activities on HBD-1 production by NHEK. CCL2 and IL-10 released from lineage(-)CD34(+)CD31(+) cells were shown to be inhibitory on the peptide production by NHEK, while these soluble factors were not produced by lineage(-)CD34(+)CD31(-) cells. After treatment with a mixture of mAbs for CCL2 and IL-10, the culture fluids of lineage(-)CD34(+)CD31(+) cells did not show any inhibitory activities on HBD-1 production by NHEK. Lineage(-)CD34(+)CD31(+) cells that appear in association with burn injuries play a role on the inhibition of antimicrobial peptide production by skin keratinocytes through the production of CCL2 and IL-10.