| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Production by Macrophages In Vitro and In Vivo and Prevent Endotoxin-Mediated Toxic Shock
*
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany;
MorphoSys, Martinsried/Munich, Germany; and
Institute of Medical Immunology, Humboldt University of Berlin, Berlin, Germany
Lipid A, the conserved portion of endotoxin, is the major mediator
of septic shock; therefore, endotoxin-neutralizing molecules could have
important clinical applications. Here we show that peptides derived
from Limulus anti-LPS factor (LALF),
bactericidal/permeability increasing protein (BPI) and
endotoxin-binding protein, bind to lipid A and block the recombinant
LALF/lipid A interaction in vitro. Because their neutralizing capacity
in vitro as well as in vivo has been limited, we created hybrid
peptides comprising two endotoxin-binding domains. The hybrid molecule
LL-10-H-14, containing endotoxin-binding domains from LALF and
endotoxin-binding protein, turned out to be the most active peptide
within the series of peptides tested here to inhibit the CD14/lipid A
interaction and is able in vitro to block the endotoxin-induced TNF-
release of murine macrophages up to 90%. Furthermore, LL-10-H-14 not
only reduced peak serum levels of TNF- of mice when preinjected but
also reduced TNF- levels when given 15 min after the endotoxin
challenge. As compared with other peptides, only LL-10-H-14 is able to
strongly decrease endotoxin-stimulated TNF- release by human
macrophage cell lines as well as by PBMC. Furthermore, the hybrid
peptide is protective against endotoxin-provoked lethal shock. As such,
LL-10-H-14 could have prophylactic and/or therapeutic properties in
humans for the management of septic shock.
This article has been cited by other articles:
|
|
 |
|
  J. Andra, T. Gutsmann, P. Garidel, and K. Brandenburg Invited review: Mechanisms of endotoxin neutralization by synthetic cationic compounds Innate Immunity, October 1, 2006; 12(5): 261 - 277. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Okuda, S. Yomogida, H. Tamura, and I. Nagaoka Determination of the Antibacterial and Lipopolysaccharide-Neutralizing Regions of Guinea Pig Neutrophil Cathelicidin Peptide CAP11. Antimicrob. Agents Chemother., August 1, 2006; 50(8): 2602 - 2607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. McMichael, A. Roghanian, L. Jiang, R. Ramage, and J.-M. Sallenave The Antimicrobial Antiproteinase Elafin Binds to Lipopolysaccharide and Modulates Macrophage Responses Am. J. Respir. Cell Mol. Biol., May 1, 2005; 32(5): 443 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Santamaria, S. Larios, S. Quiros, J. Pizarro-Cerda, J.-P. Gorvel, B. Lomonte, and E. Moreno Bactericidal and Antiendotoxic Properties of Short Cationic Peptides Derived from a Snake Venom Lys49 Phospholipase A2 Antimicrob. Agents Chemother., April 1, 2005; 49(4): 1340 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Geetha, S.G. Venkatesh, L. Bingle, C.D. Bingle, and S.-U. Gorr Design and Validation of Anti-inflammatory Peptides from Human Parotid Secretory Protein Journal of Dental Research, February 1, 2005; 84(2): 149 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsuzaki, H. Kobayashi, T. Yagyu, K. Wakahara, T. Kondo, N. Kurita, H. Sekino, K. Inagaki, M. Suzuki, N. Kanayama, et al. Bikunin Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Induction in Macrophages Clin. Vaccine Immunol., November 1, 2004; 11(6): 1140 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Silverstein Review: D-Galactosamine lethality model: scope and limitations Innate Immunity, June 1, 2004; 10(3): 147 - 162. [Abstract] [PDF]
|
|
|
|
|
|
M. d. J. Arana, M. G. Vallespi, G. Chinea, G. V. Vallespi, I. Rodriguez-Alonso, H. E. Garay, W. A. Buurman, and O. Reyes Inhibition of LPS-responses by synthetic peptides derived from LBP associates with the ability of the peptides to block LBP-LPS interaction Innate Immunity, October 1, 2003; 9(5): 281 - 291. [Abstract] [PDF]
|
|
|
|
 |
|
 E. S. Van Amersfoort, T. J. C. Van Berkel, and J. Kuiper Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock Clin. Microbiol. Rev., July 1, 2003; 16(3): 379 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Scott, D. J. Davidson, M. R. Gold, D. Bowdish, and R. E. W. Hancock The Human Antimicrobial Peptide LL-37 Is a Multifunctional Modulator of Innate Immune Responses J. Immunol., October 1, 2002; 169(7): 3883 - 3891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Nagaoka, S. Hirota, F. Niyonsaba, M. Hirata, Y. Adachi, H. Tamura, S. Tanaka, and D. Heumann Augmentation of the Lipopolysaccharide-Neutralizing Activities of Human Cathelicidin CAP18/LL-37-Derived Antimicrobial Peptides by Replacement with Hydrophobic and Cationic Amino Acid Residues Clin. Vaccine Immunol., September 1, 2002; 9(5): 972 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Augusto, J. Li, M. Synguelakis, J. Johansson, and R. Chaby Structural Basis for Interactions between Lung Surfactant Protein C and Bacterial Lipopolysaccharide J. Biol. Chem., June 21, 2002; 277(26): 23484 - 23492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Nagaoka, S. Hirota, F. Niyonsaba, M. Hirata, Y. Adachi, H. Tamura, and D. Heumann Cathelicidin Family of Antibacterial Peptides CAP18 and CAP11 Inhibit the Expression of TNF-{alpha} by Blocking the Binding of LPS to CD14+ Cells J. Immunol., September 15, 2001; 167(6): 3329 - 3338. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
