Multiple trauma induces serum production of host defence peptides

Lippross, Sebastian; Klueter, Tim; Steubesand, Nadine; Oestern, Stefanie; Mentlein, Rolf; Hildebrandt, F.; Podschun, Rainer; Pufe, Thomas; Seekamp, Andreas; Varoga, Deike

doi:10.1016/j.injury.2011.03.044

Cited by 33 publications

(26 citation statements)

References 31 publications

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“…Particularly multiply injured patients with a combination of wounds and open fractures are faced by a multiplicity of invading Gram-positive and Gram-negative bacteria. In previous investigations we showed that serum of trauma patients reveals an enhanced antimicrobial effect in comparison to healthy volunteers serum [5]. In this study we documented a significant induction of lysozyme in serum of multiply injured patients.…”

Section: Discussionsupporting

confidence: 69%

“…Further observations supported the hypothesis that small HDP were responsible for the antimicrobial effect. As possible mediators we detected an induction of the human beta-defensins 2 and 3 (hBD-2 and hBD-3) and the cathelicidin LL-37 in serum of multiply injured patients [5]. Although these HDP were significantly upregulated after trauma, the source of the high antimicrobial capacity of trauma serum could not be clarified completely.…”

Section: Introductionmentioning

confidence: 99%

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The Antimicrobial Peptide Lysozyme Is Induced after Multiple Trauma

Klüter

Fitschen-Oestern

Lippross

et al. 2014

Mediators of Inflammation

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The antimicrobial peptide lysozyme is an important factor of innate immunity and exerts high potential of antibacterial activity. In the present study we evaluated the lysozyme expression in serum of multiple injured patients and subsequently analyzed their possible sources and signaling pathways. Expression of lysozyme was examined in blood samples of multiple trauma patients from the day of trauma until 14 days after trauma by ELISA. To investigate major sources of lysozyme, its expression and regulation in serum samples, different blood cells, and tissue samples were analysed by ELISA and real-time PCR. Neutrophils and hepatocytes were stimulated with cytokines and supernatant of Staphylococcus aureus. The present study demonstrates the induction and release of lysozyme in serum of multiple injured patients. The highest lysozyme expression of all tested cells and tissues was detected in neutrophils. Stimulation with trauma-related factors such as interleukin-6 and S. aureus induced lysozyme expression. Liver tissue samples of patients without trauma show little lysozyme expression compared to neutrophils. After stimulation with bacterial fragments, lysozyme expression of hepatocytes is upregulated significantly. Toll-like receptor 2, a classic receptor of Gram-positive bacterial protein, was detected as a possible target for lysozyme induction.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

The Antimicrobial Peptide Lysozyme Is Induced after Multiple Trauma

Klüter

Fitschen-Oestern

Lippross

et al. 2014

Mediators of Inflammation

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“…This peptide is expressed in many types of immune and epithelial cells and plays multiple roles in modulating host cellular responses to microbial attack (8). The physiological concentration of LL-37 varies between different cells and tissues and is often altered at infection sites (9)(10)(11)(12). The main antibacterial functions of LL-37 disrupt the microbial cell membrane, which results in cytoplasm leakage (13).…”

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confidence: 99%

Inactivation of the Antifungal and Immunomodulatory Properties of Human Cathelicidin LL-37 by Aspartic Proteases Produced by the Pathogenic Yeast Candida albicans

et al. 2015

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c Constant cross talk between Candida albicans yeast cells and their human host determines the outcome of fungal colonization and, eventually, the progress of infectious disease (candidiasis). An effective weapon used by C. albicans to cope with the host defense system is the release of 10 distinct secreted aspartic proteases (SAPs). Here, we validate a hypothesis that neutrophils and epithelial cells use the antimicrobial peptide LL-37 to inactivate C. albicans at sites of candidal infection and that C. albicans uses SAPs to effectively degrade LL-37. LL-37 is cleaved into multiple products by SAP1 to -4, SAP8, and SAP9, and this proteolytic processing is correlated with the gradual decrease in the antifungal activity of LL-37. Moreover, a major intermediate of LL-37 cleavage-the LL-25 peptide-is antifungal but devoid of the immunomodulatory properties of LL-37. In contrast to LL-37, LL-25 did not affect the generation of reactive oxygen species by neutrophils upon treatment with phorbol esters. Stimulating neutrophils with LL-25 (rather than LL-37) significantly decreased calcium flux and interleukin-8 production, resulting in lower chemotactic activity of the peptide against neutrophils, which may decrease the recruitment of neutrophils to infection foci. LL-25 also lost the function of LL-37 as an inhibitor of neutrophil apoptosis, thereby reducing the life span of these defense cells. This study indicates that C. albicans can effectively use aspartic proteases to destroy the antimicrobial and immunomodulatory properties of LL-37, thus enabling the pathogen to survive and propagate.A s a polymorphic opportunistic fungal pathogen, Candida albicans colonizes distinct niches in the human body such as the oral and vaginal cavities and the gut. In healthy individuals, C. albicans is controlled by the host immune system, epithelial barriers, and coexisting commensal microorganisms (1). However, under certain circumstances, C. albicans causes relatively easily curable superficial infections, as well as life-threatening deepseated and disseminated candidiases (2). The transition of C. albicans from a commensal to a pathogen depends mostly on the status of the host's immune system; therefore, the major risk factors for candidiasis include immunosuppressive therapy, indwelling vascular catheters, neutropenia, and prolonged treatment with broad-spectrum antibiotics (3). The pathogenic potential of C. albicans is determined by several factors, including molecules that mediate adhesion to and invasion of host cells, secreted hydrolases, polymorphisms, biofilm formation, and adaptation to stressful environmental conditions within the host organism (4).Neutrophils, which constitute the first line of host defense against microbial pathogens, are recruited to the infection site, where they rapidly respond with diverse antimicrobial mechanisms that demonstrate both intra-and extracellular processes such as phagocytosis and the degranulation and formation of neutrophil extracellular traps (NETs) (5). All of these processes inv...

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“…Recently, these fi ndings were confi rmed in patients with multiple trauma [18]. Th e authors noted that despite open bone fractures and severe soft tissue trauma in multiple trauma, the rate of bacterial infection is surprisingly low and hypothesized that this may be related to serum concentrations of AMPs.…”

Section: Naturally Occurring Antimicrobial Peptides In Infl Ammationmentioning

confidence: 95%

“…Th e authors noted that despite open bone fractures and severe soft tissue trauma in multiple trauma, the rate of bacterial infection is surprisingly low and hypothesized that this may be related to serum concentrations of AMPs. Concentrations of HBD2, HBD3 and LL-37 were elevated after trauma suggesting a higher anti-bacterial eff ect compared to healthy donors thus explaining the relatively low infec tion rates [18].…”

Section: Naturally Occurring Antimicrobial Peptides In Infl Ammationmentioning

confidence: 96%