Severely burned patient peripheral linage– CD34+ cells are inhibitory on the antimicrobial peptide production by human epidermal keratinocytes (133.10)

Abstract

Abstract The importance of epidermal keratinocyte-produced antimicrobial peptides in the control of skin infections has been described. However, these peptides are not produced sufficiently in tissues surrounding the burn area. In this study, linage- CD34+ cells that infiltrated into burn area tissues were shown to be inhibitory on the antimicrobial peptide production by human epidermal keratinocytes (NHEK). Peripheral blood mononuclear cells (PBMC) taken from 5 severely burned patients (3rd degree, more than 40% total body surface area burn) enrolled in these experiments. NHEK (1 x 105 cells/ml, lower chamber) were cultured with 1 x 105 cells/ml of healthy donor PBMC or patient PBMC in a dual-chamber transwell. Forty-eight hrs after cultivation, cells in the lower chamber were assayed for human β-defensin-1 (HBD-1) and cathelicidin (CAP-18) mRNAs by RT-PCR. Without any stimulation, mRNAs for HBD-1 and CAP-18 were consistently expressed by NHEK. mRNA expression for HBD-1 and CAP-18 by NHEK was not influenced when peptide producer cells were transwell-cultured with normal donor PBMC. However, the expression of HBD-1 and CAP-18 mRNAs by NHEK was greatly suppressed when they were transwell-cultured with patient PBMC. Suppressor cells in patient PBMC for the peptide production by NHEK were determined to be linage- CD34+ cells. Linage- CD34+ cells isolated from healthy donor PBMC did not have any suppressor cell activities. These results indicate that linage- CD34+ cells isolated from severely burned patient PBMC are suppressor cells on the antimicrobial peptide production by epidermal keratinocytes. This study was supported by SHC NA #8610.