The Polarization of M2b Monocytes in Cultures of Burn Patient Peripheral CD14(+) Cells Treated with a Selected Human CCL1 Antisense Oligodeoxynucleotide

摘要

M2b macrophages (M phi) play a major role in the increased susceptibility of subacutely burned patients, to sepsis stemming from enterococcal translocation. Certain opportunistic infections in severely burned mice have been controlled by murine CCL1 antisense oligodeoxynucleotide (ODN), a specific polarizer of mouse M2bM phi. In the present study, we have screened CCL1 antisense ODN, which is active against human M2bM phi. Among the 20 CCL1 antisense ODNs synthesized in our laboratory, HCA-11 was shown to be the most active polarizer for human CCL1(+)CD163(+)CD14(+) cells. Burn patient CCL1(+)CD163(+)CD14(+) cells (3x10(5) cells/mL) switched to quiescent CCL1(-)CD163(-)CD14(+) cells within 48h in cultures supplemented with 100g/mL of HCA-11. After treatment with a 25g/chimera dose of HCA-11, the bacterial growth was not observed in various organs of patient chimeras (NSG mice inoculated with burn patient WBCs) infected with a lethal dose of Methicillin-resistant Staphylococcus aureus. The host antibacterial defenses against certain opportunistic pathogens should be improved in severely burned patients treated with a human CCL1 antisense ODN, HCA-11.