Innate defence of the eye by antimicrobial defensin peptides

Haynes, R J; Tighe, Patrick J.; Dua, Hs

doi:10.1016/s0140-6736(05)79185-6

Cited by 46 publications

(36 citation statements)

References 5 publications

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“…38 Recent studies have shown that the antimicrobial peptides human α-defensin (hBD)-1,-2, and -3 are expressed by ocular surface epithelia and therefore are likely to contribute to the innate immune response. [39][40][41][42][43] The goals of the current study were (1) to determine whether LL-37, like α-defensins, is secreted by corneal and conjunctival epithelia as part of the innate immune response, and (2) to assess in vitro the antimicrobial activity of LL-37 against major ocular bacterial and viral pathogens.…”

Section: Introductionmentioning

confidence: 99%

Human Cathelicidin (LL-37), a Multifunctional Peptide, is Expressed by Ocular Surface Epithelia and has Potent Antibacterial and Antiviral Activity

Gordon

Li-min

Romanowski

et al. 2005

Current Eye Research

222

190

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Purpose: This study determined whether LL-37 (cathelicidin)is expressed by conjunctival and corneal epithelia as part of ocular host defense. The antimicrobial activity of LL-37 was also assessed in vitro against Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), Staphylococcus epidermidis (SE), herpes simplex virus type 1 (HSV-1), and adenovirus (Ad). Methods: Expression of LL-37/hCAP 18 mRNA and LL-37 protein was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting, respectively, in scraped human corneal epithelium and primary cultured human corneal and conjunctival epithelial cells. The EC 50 values for three strains of PA and one each of SA and SE were determined for LL-37. LL-37 antiviral inhibition of HSV-1 and adenovirus was assessed by direct inactivation assays. Toxicity of LL-37 to A549 cells was evaluated by a MTT assay. Results: LL-37/hCAP18 mRNA and LL-37 peptide were expressed by human corneal and conjunctival epithelial cells. Antibacterial activity for LL-37 was demonstrated (EC 50 values for the three PA strains were 2.8 ± 1.3, 1.9 ± 0.3, and 3.6 ± 2.1; for SA: 1.6 ± 1.5; for SE: 1.3 ± 1.9 μg/ml). LL-37 produced a significant reduction (p < 0.001 ANOVA) in HSV-1 and Ad19 viral titers with distinctly different time-kill curves (p < 0.001). LL-37 (up to 111 μM) produced no toxicity in A549 cells. Conclusions: Corneal and conjunctival epithelia express LL-37 as part of mucosal innate immunity to protect against bacterial and viral ocular infections.

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Section: Introductionmentioning

confidence: 99%

Human Cathelicidin (LL-37), a Multifunctional Peptide, is Expressed by Ocular Surface Epithelia and has Potent Antibacterial and Antiviral Activity

Gordon

Li-min

Romanowski

et al. 2005

Current Eye Research

222

190

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“…These defenses could involve biochemical factors constitutively expressed or upregulated in response to injury or bacterial exposure. Candidate factors could include defensin or other antimicrobial peptides, secretory immunoglobulin A, and mucin glycoproteins (11,14,23).In this study we focused on surfactant protein D (SP-D), which we have previously shown is present at the ocular surface, is upregulated by P. aeruginosa or its antigens, and can protect corneal epithelial cells against invasion (27,28). Others have shown that SP-D-deficient mice lose their capacity to recover from P. aeruginosa keratitis when the eye is made susceptible using an injury model (25).…”

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confidence: 99%

mentioning

confidence: 99%

Clearance of Pseudomonas aeruginosa from a Healthy Ocular Surface Involves Surfactant Protein D and Is Compromised by Bacterial Elastase in a Murine Null-Infection Model

et al. 2009

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Our previous studies showed that surfactant protein D (SP-D) is present in human tear fluid and that it can protect corneal epithelial cells against bacterial invasion. Here we developed a novel null-infection model to test the hypothesis that SP-D contributes to the clearance of viablePseudomonas aeruginosa from the healthy ocular surface in vivo. Healthy corneas of Black Swiss mice were inoculated with 10 7 or 10 9 CFU of invasive (PAO1) or cytotoxic (6206) P. aeruginosa. Viable counts were performed on tear fluid collected at time points ranging from 3 to 14 h postinoculation. Healthy ocular surfaces cleared both P. aeruginosa strains efficiently, even when 10 9 CFU was used: e.g., <0.01% of the original inoculum was recoverable after 3 h. Preexposure of eyes to bacteria did not enhance clearance. Clearance of strain 6206 (low protease producer), but not strain PAO1 (high protease producer), was delayed in SP-D gene-targeted (SP-D ؊/؊ ) knockout mice. A protease mutant of PAO1 (PAO1 lasA lasB aprA) was cleared more efficiently than wild-type PAO1, but this difference was negligible in SP-D ؊/؊ mice, which were less able to clear the protease mutant. Experiments to study mechanisms for these differences revealed that purified elastase could degrade tear fluid SP-D in vivo. Together, these data show that SP-D can contribute to the clearance of P. aeruginosa from the healthy ocular surface and that proteases can compromise that clearance. The data also suggest that SP-D degradation in vivo is a mechanism by which P. aeruginosa proteases could contribute to virulence.Pseudomonas aeruginosa, an opportunistic pathogen, is a leading cause of bacterial keratitis. While normal, healthy human corneas remain resistant to infection, contact lens wear or corneal injury/surgery can enable susceptibility (5,15,26). The mechanisms by which these factors predispose to infection are not yet well understood.A murine scarification model has been used exclusively to study the pathogenesis of P. aeruginosa corneal infection (3,9,30). That model involves scratching the cornea with a sterile needle prior to adding bacteria, which enables bacteria to directly access the exposed stroma. The resulting disease resembles P. aeruginosa infection in people. More recently, we used a healing model of murine corneal infection to show that 6 h after scratching, the mouse cornea remains susceptible to infection, but by 12 h, it regains resistance to infection despite loss of barrier function to fluorescein staining (18). These injury models that enable P. aeruginosa to infect the cornea have led to a wealth of information about how infection develops and resulting pathology. Yet, the mechanisms by which the normal ocular surface remains healthy under normal circumstances have not been explored in vivo. This cannot be studied using a scratch model. The corneas' ability to resist disease despite constant daily exposure to potential pathogens is remarkable, and learning about the mechanisms involved could help us to develop new therapies for disea...

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“…Produzida pelas glândulas lacrimais principal e acessórias de Krause e Wolfring, transporta nutrientes solúveis em água, substâncias bactericidas, como lactoferrina, imunoglobulinas, lisozima, β-lisina e defensinas, e componentes essenciais para proliferação e diferenciação do epitélio da superfície ocular, como fator de crescimento da epiderme (EGF) e vitamina A [10][11][12][13][14][15][16] . Atualmente, é considerada como sendo essencialmente formada por secreção reflexa 2,17 .…”

Section: Camada Aquosaunclassified

Atualização no tratamento das ceratoconjuntivites cicatriciais

Gomes

2000

Arq. Bras. Oftalmol.

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Innate defence of the eye by antimicrobial defensin peptides

Cited by 46 publications

References 5 publications

Human Cathelicidin (LL-37), a Multifunctional Peptide, is Expressed by Ocular Surface Epithelia and has Potent Antibacterial and Antiviral Activity

Human Cathelicidin (LL-37), a Multifunctional Peptide, is Expressed by Ocular Surface Epithelia and has Potent Antibacterial and Antiviral Activity

Clearance of Pseudomonas aeruginosa from a Healthy Ocular Surface Involves Surfactant Protein D and Is Compromised by Bacterial Elastase in a Murine Null-Infection Model

Atualização no tratamento das ceratoconjuntivites cicatriciais

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