Zusammenfassung
Hintergrund
Antimikrobielle Peptide sind natürlich vorkommende kationische Peptidmoleküle. Die erste Verteidigungslinie der Verbrennungswunde stellt das angeborene Immunsystem dar, deren Bestandteile diese Peptide sind. Um die topische Anwendbarkeit in infizierten Verbrennungswunden zu vereinfachen wurde die Wirksamkeit in Fibrinkleber in vivo und in vitro getestet.
Material und Methoden
Nach In-vitro-Testung erhielten 15 männliche Sprague-Dawley-Ratten eine tief zweitgradige Verbrennung, wurden mit multiresistenten Pseudomonas aeruginosa infiziert und mit Protegrin-1 (PG-1; 100 μg/ml, n=5), Fibrinkleber (n=5) oder einem Gemisch aus beiden (n=5) topisch behandelt, die Wirkung wurde zuvor durch einen Radial-Diffsusions-Assay bestätigt; 24 h später wurde die verbrannte und infizierte Haut gewonnen und die Bakterienanzahl pro Gramm Haut bestimmt.
Ergebnisse
In vitro ließ sich die biologische Aktivität bestätigen. Die Gruppe aus entweder PG-1 oder Fibrinkleber zeigte in vivo keine signifikanten Unterschiede in der Bakterienanzahl, hingegen ließ sich in der Gruppe des Gemisches eine signifikante antibakterielle Wirkung nachweisen (p<0,04 und p<0,01).
Schlussfolgerungen
Eine Mischung aus dem antimikrobiellen Peptid PG-1 und Fibrinkleber reduziert die Bakterienzahl eines definierten Infektes einer IIb-Verbrennung in vivo signifikant im Vergleich zu den Kontrollgruppen.
Abstract
Background
Antimicrobial peptides are naturally occurring cationic peptides. The first-line of defense in infected burns is the innate immune system, of which antimicrobial peptides are essential parts. To facilitate their topical use in infected partial-thickness burns, the efficacy of a mixture with fibrin glue in vitro and in vivo was tested.
Methods
After in vitro tests, 15 male Sprague-Dawley rats received partial-thickness burns. Afterwards, the wounds were infected with multiresistant Pseudomonas aeruginosa. The animals received PG-1 (100 μg/ml, n=5), fibrin glue (n=5), or a mixture of both (n=5) topically. The efficacy of the materials was previously proven by radial diffusion assay. After 24 h, the infected and burned skin was harvested and quantitative bacterial counts per gram of skin performed.
Results
The biologic effect of the peptides was confirmed in vitro. The PG-1 and fibrin glue groups did not show significant differences in bacterial numbers, whereas the mixture group showed significant reduction in Pseudomonas in vivo (P<0.04 and P<0.01).
Conclusion
A mixture of an antimicrobial peptide and commercially available fibrin glue is capable of significantly reducing bacteria in infected partial thickness burns in vivo compared to controls.
Literatur
Agerberth B, Charo J, Werr J, Olsson B et al. (2000) The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96:3086–3093
Bals R (2000) [Antimicrobial peptides and peptide antibiotics]. Med Klin 95:496–502
Chalekson CP, Neumeister MW, Jaynes J (2003) Treatment of infected wounds with the antimicrobial peptide D2A21. J Trauma 54:770–774
Chen J, Falla TJ, Liu H, Hurst MA et al. (2000) Development of protegrins for the treatment and prevention of oral mucositis: structure-activity relationships of synthetic protegrin analogues. Biopolymers 55:88–98
De Y, Chen Q, Schmidt AP et al. (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192:1069–1074
Fujimoto K, Yamamura K, Osada T, Hayashi T (1997) Subcutaneous tissue distribution of vancomycin from a fibrin glue/Dacron graft carrier. J Biomed Mater Res 36:564–567
Ganz T, Metcalf JA, Gallin JI, Boxer LA, Lehrer RI (1988) Microbicidal/cytotoxic proteins of neutrophils are deficient in two disorders: Chediak-Higashi syndrome and „specific“ granule deficiency. J Clin Invest 82:552–556
Ganz T (2001) Antimicrobial proteins and peptides in host defense. Semin Respir Infect 16:4–10
Gilpin DA (1996) Calculation of a new Meeh constant and experimental determination of burn size. Burns 22:607–611
Lehrer RI, Ganz T (2002) Defensins of vertebrate animals. Curr Opin Immunol 14:96–102
Marone P, Monzillo V, Segu C, Antoniazzi E (1999) Antibiotic-impregnated fibrin glue in ocular surgery: in vitro antibacterial activity. Ophthalmologica 213:12–15
Milner SM, Cole A, Ortega MR, Bakir MH, Gulati S, Bhat S, Ganz T (2003) Inducibility of HBD-2 in acute burns and chronic conditions of the lung. Burns 29:553–555
Milner SM, Bhat S, Buja M, Gulati S, Poindexter BJ, Bick RJ (2004) Expression of human beta defensin 2 in thermal injury. Burns 30:649–654
Nishimoto K, Yamamura K, Fukase F, Kobayashi M, Nishikimi N, Komori K (2004) Subcutaneous tissue release of amikacin from a fibrin glue/polyurethane graft. J Infect Chemother 10:101–104
Nizet V, Ohtake T, Lauth X et al. (2001) Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414:454–457
Osada T, Yamamura K, Yano K, Fujimoto K, Mizuno K, Sakurai T, Nabeshima T (2000) Distribution and serum concentration of sisomicin released from fibrin glue-sealed dacron graft in the rat and human. J Biomed Mater Res 52:53–57
Patrlj L, Kocman B, Martinac M, Jadrijevic S, Sosa T, Sebecic B, Brkljacic B (2000) Fibrin glue-antibiotic mixture in the treatment of anal fistulae: experience with 69 cases. Dig Surg 17:77–80
Qu XD, Harwig SS, Shafer WM, Lehrer RI (1997) Protegrin structure and activity against Neisseria gonorrhoeae. Infect Immun 65:636–639
Steinberg DA, Lehrer RI (1997) Designer assays for antimicrobial peptides. Disputing the „one-size-fits-all“ theory. Methods Mol Biol 78:169–186
Steinstraesser L, Klein RD, Aminlari A et al. (2001) Protegrin-1 enhances bacterial killing in thermally injured skin. Crit Care Med 29:1431–1437
Thompson DF, Davis TW (1997) The addition of antibiotics to fibrin glue. South Med J 90:681–684
Zanetti M, Gennaro R, Romeo D (1995) Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett 374:1–5
Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415:389–395
Interessenkonflikt:
Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lahoda, L.U., Wang, S.C. & Vogt, P.M. Antimikrobielle Peptide und Fibrinkleber in Verbrennungen. Chirurg 77, 251–256 (2006). https://doi.org/10.1007/s00104-005-1089-8
Issue Date:
DOI: https://doi.org/10.1007/s00104-005-1089-8