Monocyte-chemotactic activity of defensins from human neutrophils.

Territo, Mary; Ganz, Tomas; Selsted, Michael E.; Lehrer, Robert I.

doi:10.1172/jci114394

Cited by 448 publications

(308 citation statements)

References 18 publications

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“…Recently, based on the classification of these four subfamilies, a systematic nomenclature system of the chemokine ligands has been formulated (2). Except for the two transmembrane-type chemokines, CX3CL1 and CXCL16, chemokines are small (8)(9)(10)(11)(12)(13)(14), mostly cationic polypeptides with two to three intramolecular disulfide bonds (1). CCL28 (also called mucosae-associated epithelial chemokine) is a recently described CC chemokine signaling via CCR10 as well as CCR3 (3,4).…”

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confidence: 99%

“…Accumulating evidence points out that chemokines and antimicrobial peptides have substantially overlapping functions (11). For example, several members of the mammalian antimicrobial proteins are capable of attracting leukocytes via interactions with selected seven-transmembrane G protein-coupled receptors (12)(13)(14). Most notably, Yang et al (15) have recently demonstrated that human ␤-defensins are potent agonists for CCR6, the receptor for the chemokine CCL20 (also called liver and activation-regulated chemokine or macrophage inflammatory protein-3␣), which is produced by mucosal epithelial cells and epidermal keratinocytes upon proinflammatory stimulations that selectively attracts immature dendritic cells, memory T cells, and B cells (1,16).…”

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confidence: 99%

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CCL28 Has Dual Roles in Mucosal Immunity as a Chemokine with Broad-Spectrum Antimicrobial Activity

Hieshima¹,

Ohtani

Shibano³

et al. 2003

The Journal of Immunology

227

268

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CCL28 is a CC chemokine signaling via CCR10 and CCR3 that is selectively expressed in certain mucosal tissues such as exocrine glands, trachea, and colon. Notably, these tissues commonly secrete low-salt fluids. RT-PCR analysis demonstrated that salivary glands expressed CCL28 mRNA at the highest levels among various mouse tissues. Single cells prepared from mouse parotid glands indeed contained a major fraction of CD3−B220low cells that expressed CCR10 at high levels and CCR3 at low levels and responded to CCL28 in chemotaxis assays. Morphologically, these cells are typical plasma cells. By immunohistochemistry, acinar epithelial cells in human and mouse salivary glands were strongly positive for CCL28. Furthermore, human saliva and milk were found to contain CCL28 at high concentrations. Moreover, the C terminus of human CCL28 has a significant sequence similarity to histatin-5, a histidine-rich candidacidal peptide in human saliva. Subsequently, we demonstrated that human and mouse CCL28 had a potent antimicrobial activity against Candida albicans, Gram-negative bacteria, and Gram-positive bacteria. The C-terminal 28-aa peptide of human CCL28 also displayed a selective candidacidal activity. In contrast, CCL27, which is most similar to CCL28 and shares CCR10, showed no such potent antimicrobial activity. Like most other antimicrobial peptides, CCL28 exerted its antimicrobial activity in low-salt conditions and rapidly induced membrane permeability in target microbes. Collectively, CCL28 may play dual roles in mucosal immunity as a chemoattractant for cells expressing CCR10 and/or CCR3 such as plasma cells and also as a broad-spectrum antimicrobial protein secreted into low-salt body fluids.

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confidence: 99%

mentioning

confidence: 99%

CCL28 Has Dual Roles in Mucosal Immunity as a Chemokine with Broad-Spectrum Antimicrobial Activity

Hieshima¹,

Ohtani

Shibano³

et al. 2003

The Journal of Immunology

227

268

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“…Defensins have antimicrobial activities against fungi, bacteria, and viruses as well as abilities to neutralize lethal anthrax toxin (6 -12). ␣-Defensins also facilitate and amplify the innate and adaptive immune responses because they can attract human CD4 ϩ CD45RA ϩ or CD8 ϩ T cells (13,14), immature dendritic cells (14), and monocytes (15). ␣-Defensins induce the release of IFN-␥, IL-6, and IL-10 from T cells, TNF-␣, and IL-1␤ from monocytes, and IL-8 from alveolar macrophages and intestinal and lung epithelial cell-lines (16 -21).…”

mentioning

confidence: 99%

Leukotriene B4 Triggers the In Vitro and In Vivo Release of Potent Antimicrobial Agents

Flamand

Tremblay

Borgeat

2007

The Journal of Immunology

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Leukotriene B4 (LTB4) is a bioactive lipid derived from the metabolism of arachidonic acid. Mainly produced by polymorphonuclear leukocytes (PMN) and macrophages, LTB4 triggers several functional responses important in host defense, including the secretion of lysosomal enzymes, the activation of NADPH oxidase activity, NO formation, and phagocytosis. We report that LTB4, but not structural analogs thereof, stimulates primed human PMN to release molecules having potent antimicrobial activities. Exposure of bacteria (Escherichia coli and Staphylococcus aureus) or viruses (herpes simplex virus type 1 and HIV type 1) to supernatants of LTB4-activated PMN lead to ≥90% reduction in infectivity. ELISA and mass spectroscopy analysis of proteins released from LTB4-activated PMN have identified several antimicrobial proteins, including α-defensins, cathepsin G, elastase, lysozyme C, and LL-37, that are likely to participate in the killing of microorganisms. In addition to these in vitro observations, i.v. injections of LTB4 (50 μg/kg) to monkeys led to an increase in α-defensin plasmatic levels and enhanced ex vivo antimicrobial activities of plasma. These results demonstrate the ability of LTB4 to cause the release of potent antimicrobial agents from PMN in vitro as well as in vivo and add further support to the important role of LTB4 in host defense.

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“…Besides the antibacterial activity of HNPs, other biological functions such as chemotactic activity to native resting T cells and dendritic cells, degranulation of mast cells, regulation of complement activation, and inhibition of glucocorticoid production have been implicated [45,47,[56][57][58][59].…”

Section: Defensinsmentioning

confidence: 99%

Innate defences against methicillin‐resistant Staphylococcus aureus (MRSA) infection

Komatsuzawa

Ouhara

Yamada

et al. 2005

The Journal of Pathology

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The innate immune system is the primary defence against bacterial infection. Among the factors involved in innate defence, anti-microbial peptides produced by humans have recently attracted attention due to their relevance to some diseases and also to the development of new chemotherapeutic agents. Staphylococcus aureus is one of the major human pathogens, causing a variety of infections from suppurative disease to food poisoning. Methicillin-resistant S. aureus (MRSA) is a clinical problem and with the recent emergence of a vancomycin-resistant strain, this will pose serious problems in the near future. In investigating the molecular biology of S. aureus infections to develop new chemotherapeutic agents against MRSA infections, knowledge of the interaction of innate anti-microbial peptides with S. aureus is important. In vitro and in vivo experiments demonstrate that exposure of S. aureus to host cells can induce the anti-microbial peptides β-defensin-2 (hBD2), hBD3, and LL37/CAP18. The induction level of these peptides differs among strains, as does the susceptibility of the strains, with MRSA strains exhibiting lower susceptibility. In summary, the susceptibility of S. aureus strains, including MRSA strains, to components of the innate immune system varies, with the MRSA strains showing more resistance to both innate immune factors and chemotherapeutic agents.

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Monocyte-chemotactic activity of defensins from human neutrophils.

Cited by 448 publications

References 18 publications

CCL28 Has Dual Roles in Mucosal Immunity as a Chemokine with Broad-Spectrum Antimicrobial Activity

CCL28 Has Dual Roles in Mucosal Immunity as a Chemokine with Broad-Spectrum Antimicrobial Activity

Leukotriene B4 Triggers the In Vitro and In Vivo Release of Potent Antimicrobial Agents

Innate defences against methicillin‐resistant Staphylococcus aureus (MRSA) infection

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