The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations.
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-alpha-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, gammadelta T-cell lines, NK clones, and one monocytic cell line, with positive results, but found no expression in several alphabeta T-cell lines. The alpha-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, gammadelta 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-gamma. 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 alpha-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.
Agerberth
B
B
Department of Medical Biochemistry and Biophysics, Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden.
Charo
J
J
Werr
J
J
Olsson
B
B
Idali
F
F
Lindbom
L
L
Kiessling
R
R
Jörnvall
H
H
Wigzell
H
H
Gudmundsson
G H
GH
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001402:B-Lymphocytes / Q000502:physiology; D002352:Carrier Proteins / Q000494:pharmacology; D054804:Cathelicidins; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D003001:Cloning, Molecular; D006657:Histones / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D009113:Muramidase / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology; D023084:alpha-Defensins / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; D006657:Histones; D015850:Interleukin-6; D023084:alpha-Defensins; D007371:Interferon-gamma; D009113:Muramidase