HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 34, 36072-36082, August 20, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/34/36072    most recent M314264200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bocharov, A. V. Articles by Eggerman, T. L. Search for Related Content PubMed PubMed Citation Articles by Bocharov, A. V. Articles by Eggerman, T. L. Social Bookmarking                      What's this?

Targeting of Scavenger Receptor Class B Type I by Synthetic Amphipathic -Helical-containing Peptides Blocks Lipopolysaccharide (LPS) Uptake and LPS-induced Pro-inflammatory Cytokine Responses in THP-1 Monocyte Cells^*

Alexander V. Bocharov, Irina N. Baranova, Tatyana G. Vishnyakova, Alan T. Remaley, Gyorgy Csako, Fairwell Thomas, Amy P. Patterson, and Thomas L. Eggerman¶||

From the Department of Laboratory Medicine, W. G. Magnuson Clinical Center, NHLBI, and the ^¶Division of Diabetes, Endocrinology and Metabolic Diseases, NIDDK, the National Institutes of Health, Bethesda, Maryland 20892

Human scavenger receptor class B type I, CLA-1, mediates lipopolysaccharide (LPS) binding and internalization (Vishnyakova, T. G., Bocharov, A. V., Baranova, I. N., Chen, Z., Remaley, A. T., Csako, G., Eggerman, T. L., and Patterson, A. P. (2003) J. Biol. Chem. 278, 22771–22780). Because one of the recognition motifs in SR-B1 ligands is the anionic amphipathic -helix, we analyzed the effects of model amphipathic -helical-containing peptides on LPS uptake and LPS-stimulated cytokine production. The L-37pA model peptide, containing two class A amphipathic helices, bound with high affinity (K_d = 0.94 µg/ml) to CLA-1-expressing HeLa cells with a 10-fold increased capacity when compared with mock transfected HeLa cells. Both LPS and L-37pA colocalized with anti-CLA-1 antibody and directly bound CLA-1 as determined by cross-linking. SR-BI/CLA-1 ligands such as HDL, apoA-I, and L-37pA efficiently competed against iodinated L-37pA. Bacterial LPS, lipoteichoic acid, and hsp60 also competed against iodinated L-37pA. Model peptides blocked uptake of iodinated LPS in both mock transfected and CLA-1-overexpressing HeLa cells. Bound and internalized Alexa-L-37pA and BODIPY-LPS colocalized at the cell surface and perinuclear compartment. Both ligands were predominantly transported to the Golgi complex, colocalizing with the Golgi markers bovine serum albumin-ceramide, anti-Golgin97 antibody, and cholera toxin subunit B. A 100-fold excess of L-37pA nearly eliminated BODIPY-LPS binding and internalization. L-37pA and its D-amino acid analogue, D-37pA peptide were similarly effective in blocking LPS, Gram-positive bacterial wall component lipoteichoic acid and bacterial heat shock protein Gro-EL-stimulated cytokine secretion in THP-1 cells. In the same culture media used for the cytokine stimulation study, neither L-37pA nor D-37pA affected the Limulus amebocyte lysate activity of LPS, indicating that LPS uptake and cytokine stimulation were blocked independently of LPS neutralization. These results demonstrate that amphipathic helices of exchangeable apolipoproteins may represent a general host defense mechanism against inflammation.

Received for publication, December 29, 2003 , and in revised form, May 17, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: the Division of Diabetes, Endocrinology and Metabolic Diseases, NIDDK, National Institutes of Health, 6707 Democracy Blvd., Rm. 697, MSC5460 Bethesda, MD 20892-5460. Tel.: 301-594-8813; Fax: 301-480-3503; E-mail: eggermant{at}extra.niddk.nih.gov (T. L. E.) or abocharov{at}mail.cc.nih.gov (A. V. B.).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. N. Baranova, R. Kurlander, A. V. Bocharov, T. G. Vishnyakova, Z. Chen, A. T. Remaley, G. Csako, A. P. Patterson, and T. L. Eggerman Role of Human CD36 in Bacterial Recognition, Phagocytosis, and Pathogen-Induced JNK-Mediated Signaling J. Immunol., November 15, 2008; 181(10): 7147 - 7156. [Abstract] [Full Text] [PDF]

				Y. Zhang, A. M. Ahmed, N. McFarlane, C. Capone, D. R. Boreham, R. Truant, S. A. Igdoura, and B. L. Trigatti Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathways J. Lipid Res., February 1, 2007; 48(2): 405 - 416. [Abstract] [Full Text] [PDF]

				T. G. Vishnyakova, R. Kurlander, A. V. Bocharov, I. N. Baranova, Z. Chen, M. S. Abu-Asab, M. Tsokos, D. Malide, F. Basso, A. Remaley, et al. CLA-1 and its splicing variant CLA-2 mediate bacterial adhesion and cytosolic bacterial invasion in mammalian cells PNAS, November 7, 2006; 103(45): 16888 - 16893. [Abstract] [Full Text] [PDF]

				K. A. Walton, B. G. Gugiu, M. Thomas, R. J. Basseri, D. R. Eliav, R. G. Salomon, and J. A. Berliner A role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation products J. Lipid Res., September 1, 2006; 47(9): 1967 - 1974. [Abstract] [Full Text] [PDF]

				S. Abe-Dohmae, K. H. Kato, Y. Kumon, W. Hu, H. Ishigami, N. Iwamoto, M. Okazaki, C.-A. Wu, M. Tsujita, K. Ueda, et al. Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner J. Lipid Res., July 1, 2006; 47(7): 1542 - 1550. [Abstract] [Full Text] [PDF]

				T. A. Pagler, S. Rhode, A. Neuhofer, H. Laggner, W. Strobl, C. Hinterndorfer, I. Volf, M. Pavelka, E. R. M. Eckhardt, D. R. van der Westhuyzen, et al. SR-BI-mediated High Density Lipoprotein (HDL) Endocytosis Leads to HDL Resecretion Facilitating Cholesterol Efflux J. Biol. Chem., April 21, 2006; 281(16): 11193 - 11204. [Abstract] [Full Text] [PDF]

				E. Yamada, M. Montoya, C. G. Schuettler, T. P. Hickling, A. W. Tarr, A. Vitelli, J. Dubuisson, A. H. Patel, J. K. Ball, and P. Borrow Analysis of the binding of hepatitis C virus genotype 1a and 1b E2 glycoproteins to peripheral blood mononuclear cell subsets J. Gen. Virol., September 1, 2005; 86(9): 2507 - 2512. [Abstract] [Full Text] [PDF]

				Y. Liu, S. Walter, M. Stagi, D. Cherny, M. Letiembre, W. Schulz-Schaeffer, H. Heine, B. Penke, H. Neumann, and K. Fassbender LPS receptor (CD14): a receptor for phagocytosis of Alzheimer's amyloid peptide Brain, August 1, 2005; 128(8): 1778 - 1789. [Abstract] [Full Text] [PDF]

				I. N. Baranova, T. G. Vishnyakova, A. V. Bocharov, R. Kurlander, Z. Chen, M. L. Kimelman, A. T. Remaley, G. Csako, F. Thomas, T. L. Eggerman, et al. Serum Amyloid A Binding to CLA-1 (CD36 and LIMPII Analogous-1) Mediates Serum Amyloid A Protein-induced Activation of ERK1/2 and p38 Mitogen-activated Protein Kinases J. Biol. Chem., March 4, 2005; 280(9): 8031 - 8040. [Abstract] [Full Text] [PDF]