Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages

Lehrer, Robert I.; Selsted, Michael E.; Szklarek, D; Fleischmann, Jacob

doi:10.1128/iai.42.1.10-14.1983

Cited by 117 publications

(47 citation statements)

References 11 publications

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“…Interestingly, human alveolar macrophages expressed mRNA for hBD-3 upon activation with IFN-c and LPS. Our observation that alveolar macrophages, but not monocytes and MDM, express a particular antimicrobial peptide is certainly not unique, since alveolar macrophages in rabbits 45 produced antimicrobial peptides not found in other types of mononuclear phagocytes.…”

Section: Discussionmentioning

confidence: 69%

Expression of β‐defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells

Duits

Ravensbergen²,

Rademaker³

et al. 2002

Immunology

232

157

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SUMMARYHuman b-defensins are broad-spectrum antimicrobial peptides known to be produced by epithelial cells. It was recently shown that b-defensins also display chemotactic activity for dendritic cells (DC) and T cells, and thus may serve to link innate and adaptive immunity. The aim of the present study was to explore expression of mRNA for these peptides in mononuclear phagocytes and DC. The results revealed that monocytes, monocyte-derivedmacrophages (MDM), and monocyte-derived-dendritic cells (DC) all express humanb-defensin-1 (hBD-1) mRNA. hBD-1 mRNA expression by monocytes and MDM was increased after activation with interferon-c (IFN-c) and/or lipopolysaccharide (LPS) in a dose-and time-dependent fashion. Alveolar macrophages showed an intense hBD-1 expression, which could not be further increased. Expression of hBD-1 mRNA by immature DC was low, and increased considerably after maturation. Monocytes, MDM, alveolar macrophages and DC showed a limited expression of human b-defensin-2 (hBD-2) mRNA, which could only be increased in monocytes and alveolar macrophages by IFN-c and/or LPS in a dose-and time-dependent fashion. Immunocytochemical stainings demonstrated the expression of hBD-2 peptide by freshly isolated blood monocytes and alveolar macrophages in cytospin preparations.

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Section: Discussionmentioning

confidence: 69%

Expression of β‐defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells

Duits

Ravensbergen²,

Rademaker³

et al. 2002

Immunology

232

157

View full text Add to dashboard Cite

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“…Bactericidal kinetics was determined using a modified version of the assay described by Lehrer et al [20]. CP1 at the MIC concentration of 3 µM was incubated with 10 5 CFU/ml for 30 min.…”

Section: Antimicrobial Activitymentioning

confidence: 99%

Membrane permeability and antimicrobial kinetics of cecropin P1 against Escherichia coli

Arcidiacono

Soares

Meehan

et al. 2009

Journal of Peptide Science

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The interaction of cecropin P1 (CP1) with Escherichiacoli was investigated to gain insight into the time-dependent antimicrobial action. Biophysical characterizations of CP1 with whole bacterial cells were performed using both fluorescent and colorimetric assays to investigate the role of membrane permeability and lipopolysaccharide (LPS) binding in lytic behavior. The kinetics of CP1 growth inhibition assays indicated a minimal inhibitory concentration (MIC) of 3 microM. Bactericidal kinetics at the MIC indicated rapid killing of E.coli (<30 min). Membrane permeability studies illustrated permeation as a time-dependent event. Maximum permeability at the MIC occurred within 30 min, which correlates to the bactericidal action. Further investigation showed that the immediate permeabilizing action of CP1 is concentration-dependent, which correlates to the concentration-dependent nature of the inhibition assays. At the MIC and above, the immediate permeability was significant enough that the cells could not recover and exhibit growth. Below the MIC, immediate permeability was evident, but the level was insufficient to inhibit growth. Dansyl polymyxin B displacement studies showed LPS binding is essentially the same at all concentrations investigated. However, it does appear that only the immediate interaction is important, because binding continued to increase over time beyond cell viability. Our studies correlated CP1 bactericidal kinetics to membrane permeability suggesting CP1 concentration-dependent killing is driven by the extent of the immediate permeabilizing action of the peptide.

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“…First characterized as granule components of phagocytic leukocytes (25), defensins are 3-4 kDa cationic peptides with well-characterizedantimicrobialactivities (26). Six invariantly placed cysteine residues form disulfide bonds between Cys'-Cys6, Cys2-Cys4, and Cys3-Cys5 (see Fig.…”

Section: Defensinsmentioning

confidence: 99%

Paneth cell defensins: Endogenous peptide components of intestinal host defense

1996

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Paneth cells are epithelial granulocytes at the base of the crypts of Lieberkühn in the small intestine of many mammalian species. These secretory cells contribute to mucosal barrier function by the apical release of granules containing a variety of antimicrobial products, including peptides termed cryptdins, for crypt defensins. In mice, six Paneth cell defensins have been characterized at the peptide level that have potent antimicrobial activities equivalent to or greater than that of rabbit neutrophil defensin NP-1. Cryptdin peptides that differ only by single amino acid substitutions have been shown to exhibit a high degree of specificity against certain target microorganisms. Cryptdins are coded by separate, two-exon genes that are located on chromosome 8 in both mice and humans. Human Paneth cells contain high levels of two different defensin mRNAs, but in mice at least 19 cryptdin isoforms are predicted from cDNA sequencing data. The mouse cryptdin-4 gene is expressed with positional specificity along the longitudinal intestinal axis, and cryptdin genes are active in the intestinal epithelium prior to Paneth cell differentiation. Accordingly, Paneth cell defensins are early markers of crypt ontogeny and are therefore useful in studies of lineage determination in the intestinal epithelium. Because cryptdins mediate innate immunity in the hostile environment of the intestinal lumen, it should be of interest to define biochemical and biophysical attributes that adapt these peptides to barrier function of mucosal surfaces.

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Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages

Cited by 117 publications

References 11 publications

Expression of β‐defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells

Expression of β‐defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells

Membrane permeability and antimicrobial kinetics of cecropin P1 against Escherichia coli

Paneth cell defensins: Endogenous peptide components of intestinal host defense

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