The human antimicrobial and chemotactic peptides LL-37 and α-defensins are expressed by specific lymphocyte and monocyte populations

• Published in: Blood 2000-11, Vol.96 (9), p.3086-3093
• Main Authors: Agerberth, Birgitta, Charo, Jehad, Werr, Joachim, Olsson, Berit, Idali, Farah, Lindbom, Lennart, Kiessling, Rolf, Jörnvall, Hans, Wigzell, Hans, Gudmundsson, Gudmundur H.
• Format: Article
• Language: English
• Subjects: alpha-Defensins - genetics; alpha-Defensins - pharmacology; alpha-Defensins - physiology; Analysis of the immune response. Humoral and cellular immunity; Anti-Bacterial Agents - pharmacology; Antimicrobial Cationic Peptides; B-Lymphocytes - physiology; Biological and medical sciences; Carrier Proteins - pharmacology; Cathelicidins; Cell Line; Chemotaxis, Leukocyte; Cloning, Molecular; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histones - genetics; Humans; Immunobiology; Immunohistochemistry; In Vitro Techniques; Interferon-gamma - pharmacology; Interleukin-6 - pharmacology; Killer Cells, Natural - physiology; Lymphocyte Activation; Lymphocytes - drug effects; Lymphocytes - physiology; Monocytes - physiology; Muramidase - genetics; Neutrophils - drug effects; Neutrophils - physiology; Organs and cells involved in the immune response; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - physiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V96.9.3086

We identified antibacterial components in human T and natural killer (NK) cells by using freshly isolated lymphocytes enriched for T and NK cells as starting material. After growing these lymphocytes for 5 days in the presence of interleukin (IL)–2, we isolated and characterized several antibacterial peptides/proteins from the supernatant—α-defensins (HNP 1-3), LL-37, lysozyme, and a fragment of histone H2B—although other active components were also present. We then used reverse transcriptase–polymerase chain reaction to search for expression of the gene coding for LL-37 in several B-cell lines, γδ T-cell lines, NK clones, and one monocytic cell line, with positive results, but found no expression in several αβ T-cell lines. The α-defensins (HNP 1-3) were also found to be expressed in several of these cell lines. To confirm the presence of these antibacterial peptides in lymphocytes, we localized them to NK, γδ T cells, B cells, and monocytes/macrophages by using double-staining immunohistochemical analysis of freshly isolated lymphocytes. We also found that primary cultures of lymphocytes transcribe and secrete LL-37 and that these processes are affected by IL-6 and interferon-γ. In addition, we demonstrated that LL-37 has chemotactic activity for polymorphonuclear leukocytes and CD4 T lymphocytes, whereas others have shown chemotactic activity for human α-defensins (HNP 1-2). These findings suggest that microbicidal peptides are effector molecules of lymphocytes and that antibacterial activity previously shown to be derived from T and NK cells may be partly mediated by the antibacterial peptides LL-37 and HNP 1-3.