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.

[1]  Schroder Jens-M. Epithelial Peptide Antibiotics : Local Host Response Elements of Innate Defense , 2000 .

[2]  G. H. Gudmundsson,et al.  Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system. , 1999, Journal of immunological methods.

[3]  Ji Ming Wang,et al.  β-Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6 , 1999 .

[4]  L. Matrisian,et al.  Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. , 1999, Science.

[5]  P. Murray Defining the requirements for immunological control of mycobacterial infections. , 1999, Trends in microbiology.

[6]  H. Jörnvall,et al.  Antibacterial components in bronchoalveolar lavage fluid from healthy individuals and sarcoidosis patients. , 1999, American journal of respiratory and critical care medicine.

[7]  H. Wigzell,et al.  Role of innate and adaptive immunity in the outcome of primary infection with Chlamydia pneumoniae, as analyzed in genetically modified mice. , 1999, Journal of immunology.

[8]  J. Lillard,et al.  Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[9]  T. Ganz,et al.  An antimicrobial activity of cytolytic T cells mediated by granulysin. , 1998, Science.

[10]  R. Bals,et al.  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. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[11]  K. Bailey,et al.  Potential Role of Epithelial Cell-Derived Histone H1 Proteins in Innate Antimicrobial Defense in the Human Gastrointestinal Tract , 1998, Infection and Immunity.

[12]  K. Berndt,et al.  Conformation-dependent Antibacterial Activity of the Naturally Occurring Human Peptide LL-37* , 1998, The Journal of Biological Chemistry.

[13]  D. Andreu,et al.  Animal antimicrobial peptides: an overview. , 1998, Biopolymers.

[14]  T. Ganz,et al.  Antimicrobial peptides of phagocytes and epithelia. , 1997, Seminars in hematology.

[15]  J. Cowland,et al.  An ELISA for hCAP-18, the cathelicidin present in human neutrophils and plasma. , 1997, Journal of immunological methods.

[16]  M. Ackermann,et al.  Epithelial antibiotic induced in states of disease. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Schröder,et al.  A peptide antibiotic from human skin , 1997, Nature.

[18]  H. Wigzell,et al.  The Expression of the Gene Coding for the Antibacterial Peptide LL-37 Is Induced in Human Keratinocytes during Inflammatory Disorders* , 1997, The Journal of Biological Chemistry.

[19]  R. Lehrer,et al.  Widespread expression of beta‐defensin hBD‐1 in human secretory glands and epithelial cells , 1996, FEBS letters.

[20]  J. Odeberg,et al.  The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. , 1996, European journal of biochemistry.

[21]  E. Greenberg,et al.  Cystic Fibrosis Airway Epithelia Fail to Kill Bacteria Because of Abnormal Airway Surface Fluid , 1996, Cell.

[22]  D. Taub,et al.  Identification of Defensin-1, Defensin-2, and CAP37/Azurocidin as T-cell Chemoattractant Proteins Released from Interleukin-8-stimulated Neutrophils (*) , 1996, The Journal of Biological Chemistry.

[23]  Christopher C. Goodnow,et al.  C3d of Complement as a Molecular Adjuvant: Bridging Innate and Acquired Immunity , 1996, Science.

[24]  S. Akira,et al.  Targeted Disruption of the IL‐6 Related Genes: gp130 and NF‐IL‐6 , 1995, Immunological reviews.

[25]  Domenico Romeo,et al.  Cathelicidins: a novel protein family with a common proregion and a variable C‐terminal antimicrobial domain , 1995, FEBS letters.

[26]  H. Mathews,et al.  Direct antimicrobial activity of T cells. , 1995, Immunology today.

[27]  V. Mutt,et al.  NK‐lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity. , 1995, The EMBO journal.

[28]  J. Odeberg,et al.  FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[29]  R. Lehrer,et al.  Antimicrobial proteins of murine macrophages , 1993, Infection and immunity.

[30]  Douglas E. Jones,et al.  Defensin‐6 mRNA in human Paneth cells: implications for antimicrobia peptides in host defense of the human bowel , 1993, FEBS letters.

[31]  G. Sonnenfeld,et al.  Interferon‐gamma and resistance to bacterial infections , 1993, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[32]  R I Lehrer,et al.  Defensins: antimicrobial and cytotoxic peptides of mammalian cells. , 1993, Annual review of immunology.

[33]  Douglas E. Jones,et al.  Paneth cells of the human small intestine express an antimicrobial peptide gene. , 1992, The Journal of biological chemistry.

[34]  P. García-Peñarrubia,et al.  Experimental and theoretical kinetics study of antibacterial killing mediated by human natural killer cells. , 1989, Journal of immunology.

[35]  R. O. Kelley,et al.  Antibacterial activity of human natural killer cells , 1989, The Journal of experimental medicine.

[36]  M. Frohman,et al.  Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[37]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[38]  W. N. Burnette,et al.  "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. , 1981, Analytical biochemistry.