Peptides derived from the human laminin α4 and α5 chains exhibit antimicrobial activity

Senyürek, Ilknur; Klein, Gerd; Kalbacher, Hubert; Deeg, Martin; Schittek, Birgit

doi:10.1016/j.peptides.2010.04.016

Cited by 20 publications

(14 citation statements)

References 12 publications

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“…In this scenario a repertoire of antimicrobial activity is beneficial to reduce the susceptibility of the tissue for infection. Indeed, during the past years evidence has emerged that connective tissues possess antimicrobial peptides related to extracellular matrix molecules as part of the natural tissue immune response [6,21,22,23]. Our data indicate that subepithelial collagen VI scaffolds, encoding both adhesive and antimicrobial properties, provide environments that may enhance innate antimicrobial protection in the respiratory tract.…”

Section: Discussionmentioning

confidence: 70%

Collagen VI Encodes Antimicrobial Activity: Novel Innate Host Defense Properties of the Extracellular Matrix

et al. 2012

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Collagen type VI is a subepithelial extracellular matrix component in airways and an adhesive substrate for oral pathogens [Bober et al.: J Innate Immun 2010;2:160–166]. Here, we report that collagen VI displays a dose-dependent antimicrobial activity against group A, C, and G streptococci by membrane disruption in physiological conditions. The data disclose previously unrecognized aspects of the extracellular matrix in innate host defense.

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Section: Discussionmentioning

confidence: 70%

Collagen VI Encodes Antimicrobial Activity: Novel Innate Host Defense Properties of the Extracellular Matrix

et al. 2012

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“…Laminin-332 is proteolytically processed and its extracellular mature form lacks the α3 chain C-terminal globules 4 and 5 (LG4-5). The LG4-5 tandem has keratinocyte adhesion and migration properties [23] and antimicrobial activity [24]. Interestingly, 24 h after SWT, in lysates of HaCaT keratinocytes, LG4-5 tandem modules were detected at decreasing concentrations in a dose-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 99%

Extracorporal Shock Waves Activate Migration, Proliferation and Inflammatory Pathways in Fibroblasts and Keratinocytes, and Improve Wound Healing in an Open-Label, Single-Arm Study in Patients with Therapy-Refractory Chronic Leg Ulcers

Aschermann

Noor

Venturelli

et al. 2017

Cell Physiol Biochem

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Background/Aims: Chronic leg ulcers (CLUs) are globally a major cause of morbidity and mortality with increasing prevalence. Their treatment is highly challenging, and many conservative, surgical or advanced therapies have been suggested, but with little overall efficacy. Since the 1980s extracorporal shock wave therapy (ESWT) has gained interest as treatment for specific indications. Here, we report that patients with CLU showed wound healing after ESWT and investigated the underlying molecular mechanisms. Methods: We performed cell proliferation and migration assays, FACS- and Western blot analyses, RT-PCR, and Affymetrix gene expression analyses on human keratinocytes and fibroblasts, and a tube formation assay on human microvascular endothelial cells to assess the impact of shock waves in vitro. In vivo, chronic therapy-refractory leg ulcers were treated with ESWT, and wound healing was assessed. Results: Upon ESWT, we observed morphological changes and increased cell migration of keratinocytes. Cell-cycle regulatory genes were upregulated, and proliferation induced in fibroblasts. This was accompanied by secretion of pro-inflammatory cytokines from keratinocytes, which are known to drive wound healing, and a pro-angiogenic activity of endothelial cells. These observations were transferred “from bench to bedside”, and 60 consecutive patients with 75 CLUs with different pathophysiologies (e.g. venous, mixed arterial-venous, arterial) were treated with ESWT. In this setting, 41% of ESWT-treated CLUs showed complete healing, 16% significant improvement, 35% improvement, and 8% of the ulcers did not respond to ESWT. The induction of healing was independent of patient age, duration or size of the ulcer, and the underlying pathophysiology. Conclusions: The efficacy of ESWT needs to be confirmed in controlled trials to implement ESWT as an adjunct to standard therapy or as a stand-alone treatment. Our results suggest that EWST may advance the treatment of chronic, therapy-refractory ulcers.

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“…Indeed, the results presented in this work show that different pulmonary pathogens are rapidly killed by collagen VI microfibrils, suggesting an important role of this molecule in host defense in vivo. Similarly, host defense properties of the basement membrane protein laminin have recently been described [30,31], highlighting the emerging position of connective tissue components in the field of innate immunity. However, the exact molecular mechanisms underlying such properties of collagen VI in vivo are still elusive and beyond the scope of this work.…”

Section: Discussionmentioning

confidence: 99%

Collagen VI Is Upregulated in COPD and Serves Both as an Adhesive Target and a Bactericidal Barrier for <b><i>Moraxella catarrhalis</i></b>

Abdillahi

Bober²,

Nordin

et al. 2015

J Innate Immun

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Moraxella catarrhalis is a Gram-negative human mucosal commensal and pathogen. It is a common cause of exacerbation in chronic obstructive pulmonary disease (COPD). During the process of infection, host colonization correlates with recognition of host molecular patterns. Importantly, in COPD patients with compromised epithelial integrity the underlying extracellular matrix is exposed and provides potential adhesive targets. Collagen VI is a ubiquitous fibrillar component in the airway mucosa and has been attributed both adhesive and killing properties against Gram-positive bacteria. However, less is known regarding Gram-negative microorganisms. Therefore, in the present study, the interaction of M. catarrhalis with collagen VI was characterized. We found that collagen VI is upregulated in the airways of COPD patients and exposed upon epithelial desquamation. Ex vivo, we inoculated airway biopsies and fibroblasts from COPD patients with M. catarrhalis. The bacteria specifically adhered to collagen VI-containing matrix fibrils. In vitro, purified collagen VI microfibrils bound to bacterial surface structures. The primary adhesion target was mapped to the collagen VI α₂-chain. Upon exposure to collagen VI, bacteria were killed by membrane destabilization in physiological conditions. These previously unknown properties of collagen VI provide novel insights into the extracellular matrix innate immunity by quickly entrapping and killing pathogen intruders.

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Peptides derived from the human laminin α4 and α5 chains exhibit antimicrobial activity

Cited by 20 publications

References 12 publications

Collagen VI Encodes Antimicrobial Activity: Novel Innate Host Defense Properties of the Extracellular Matrix

Collagen VI Encodes Antimicrobial Activity: Novel Innate Host Defense Properties of the Extracellular Matrix

Extracorporal Shock Waves Activate Migration, Proliferation and Inflammatory Pathways in Fibroblasts and Keratinocytes, and Improve Wound Healing in an Open-Label, Single-Arm Study in Patients with Therapy-Refractory Chronic Leg Ulcers

Collagen VI Is Upregulated in COPD and Serves Both as an Adhesive Target and a Bactericidal Barrier for <b><i>Moraxella catarrhalis</i></b>

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