title: The Polarization of M2b Monocytes in Cultures of Burn Patient Peripheral CD14+Cells Treated with a Selected Human CCL1 Antisense Oligodeoxynucleotide.
abstract: M2b macrophages (Mφ) 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 M2bMφ. In the present study, we have screened CCL1 antisense ODN, which is active against human M2bMφ. 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 (3 × 105cells/mL) switched to quiescent CCL1-CD163-CD14+cells within 48 h in cultures supplemented with 100 μg/mL of HCA-11. After treatment with a 25 μg/chimera dose of HCA-11, the bacterial growth was not observed in various organs of patient chimeras (γNSG 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.
authors.affiliation: 1 Department of Internal Medicine, The University of Texas Medical Branch , Galveston, Texas.
authors.forename: Ichiaki
authors.initials: I
authors.lastname: Ito
authors.affiliation: 1 Department of Internal Medicine, The University of Texas Medical Branch , Galveston, Texas.
authors.forename: Kamlesh K
authors.initials: KK
authors.lastname: Bhopale
authors.affiliation: 1 Department of Internal Medicine, The University of Texas Medical Branch , Galveston, Texas.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishiguchi
authors.affiliation: 2 Shriners Hospitals for Children , Galveston, Texas.
authors.forename: Jong O
authors.initials: JO
authors.lastname: Lee
authors.affiliation: 2 Shriners Hospitals for Children , Galveston, Texas.
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.affiliation: 3 University of North Texas Health Science Center , Fort Worth, Texas.
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: 4 Department of Pharmacology and Toxicology, The University of Texas Medical Branch , Galveston, Texas.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Sowers
authors.affiliation: 1 Department of Internal Medicine, The University of Texas Medical Branch , Galveston, Texas.|2 Shriners Hospitals for Children , Galveston, Texas.
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: 1 Department of Internal Medicine, The University of Texas Medical Branch , Galveston, Texas.|2 Shriners Hospitals for Children , Galveston, Texas.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000293:Adolescent; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000276:immunology; D001665:Binding Sites; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D054402:Chemokine CCL1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D002648:Child; D015870:Gene Expression; D006801:Humans; D007962:Leukocytes / Q000382:microbiology / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D051379:Mice; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use*; D009894:Opportunistic Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C065971:CCL1 protein, human; D000098902:CD163 Antigen; C502258:Ccl1 protein, mouse; D054402:Chemokine CCL1; D018950:Lipopolysaccharide Receptors; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011956:Receptors, Cell Surface