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

被引:642
作者
Agerberth, B
Charo, J
Werr, J
Olsson, B
Idali, F
Lindbom, L
Kiessling, R
Jörnvall, H
Wigzell, H
Gudmundsson, GH
机构
[1] Karolinska Inst, Microbiol & Tumorbiol Ctr, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden
[3] Karolinska Hosp, Canc Res Ctr, S-10401 Stockholm, Sweden
[4] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden
关键词
D O I
10.1182/blood.V96.9.3086.h8003086_3086_3093
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
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, gamma delta T-cell lines, NK clones, and one monocytic cell line, with positive results, but found no expression in several alpha beta 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, gamma delta 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. (C) 2000 by The American Society of Hematology.
引用
收藏
页码:3086 / 3093
页数:8
相关论文
共 40 条
[1]
Antibacterial components in bronchoalveolar lavage fluid from healthy in individuals and sarcoidosis patients [J].
Agerberth, B ;
Grunewald, J ;
Castaños-Velez, E ;
Olsson, B ;
Jörnvall, H ;
Wigzell, H ;
Eklund, A ;
Gudmundsson, GH .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1999, 160 (01) :283-290
[2]
FALL-39, A PUTATIVE HUMAN PEPTIDE ANTIBIOTIC, IS CYSTEINE-FREE AND EXPRESSED IN BONE-MARROW AND TESTIS [J].
AGERBERTH, B ;
GUNNE, H ;
ODEBERG, J ;
KOGNER, P ;
BOMAN, HG ;
GUDMUNDSSON, GH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (01) :195-199
[3]
Targeted disruption of the IL-6 related genes: gp130 and NF-IL-6 [J].
Akira, S ;
Yoshida, K ;
Tanaka, T ;
Taga, T ;
Kishimoto, T .
IMMUNOLOGICAL REVIEWS, 1995, 148 :221-253
[4]
NK-LYSIN, A NOVEL EFFECTOR PEPTIDE OF CYTOTOXIC T-CELLS AND NK-CELLS - STRUCTURE AND CDNA CLONING OF THE PORCINE FORM, INDUCTION BY INTERLEUKIN-2, ANTIBACTERIAL AND ANTITUMOR-ACTIVITY [J].
ANDERSSON, M ;
GUNNE, H ;
AGERBERTH, B ;
BOMAN, A ;
BERGMAN, T ;
SILLARD, R ;
JORNVALL, H ;
MUTT, V ;
OLSSON, B ;
WIGZELL, H ;
DAGERLIND, A ;
BOMAN, HG ;
GUDMUNDSSON, GH .
EMBO JOURNAL, 1995, 14 (08) :1615-1625
[5]
Andreu D, 1998, BIOPOLYMERS, V47, P415, DOI 10.1002/(SICI)1097-0282(1998)47:6<415::AID-BIP2>3.0.CO
[6]
2-D
[7]
The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface [J].
Bals, R ;
Wang, XR ;
Zasloff, M ;
Wilson, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (16) :9541-9546
[8]
BURNETTE WN, 1981, ANAL BIOCHEM, V112, P195, DOI 10.1016/0003-2697(81)90281-5
[9]
Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils [J].
Chertov, O ;
Michiel, DF ;
Xu, LL ;
Wang, JM ;
Tani, K ;
Murphy, WJ ;
Longo, DL ;
Taub, DD ;
Oppenheim, JJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (06) :2935-2940
[10]
CZAMIECKI CW, 1993, APMIS, V101, P1