|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 50, 46864-46869, December 14, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of In the vessel wall, macrophages are among the
cells that upon activation contribute to the atherosclerotic process.
Low density lipoproteins (LDL) can mediate this activation but only
after enzymatic or oxidative modification. Lipoprotein(a) (Lp(a)) is an
LDL variant that has been shown to have an atherogenic potential by no
clearly established mechanisms. In the present study we examined
whether native Lp(a) can activate macrophages and, if so, identify the
structural elements involved in this action. For this purpose, we
utilized human THP-1 macrophages, prepared by treating THP-1 monocytes
with phorbol ester, and we exposed them to Lp(a) and its two
derivatives, apo(a)-free LDL (Lp(a
Stimulation of Interleukin-8 Production in Human THP-1
Macrophages by Apolipoprotein(a)
EVIDENCE FOR A CRITICAL INVOLVEMENT OF ELEMENTS IN ITS
C-TERMINAL DOMAIN*
,, and§¶
Medicine and of
§ Biochemistry and Molecular Biology, University of Chicago,
Chicago, Illinois 60637
)) and free apo(a). We also studied
apo(a) fragments, F1 (N terminus) and F2 (C terminus) and subfragments
thereof, obtained by leukocyte elastase digestion. By Northern blot
analyses, Lp(a), but not Lp(a), caused up to a 12-fold increase in
interleukin 8 (IL-8) mRNA as compared with untreated cells. Free
apo(a) also induced the production of IL-8 mRNA; however, the
effect was 3-4-fold higher than that of Lp(a). The increase in
mRNA was associated with the accumulation of IL-8 protein in the
culture medium. F1 had only a minimal effect, whereas F2 was
1.5-2-fold more potent than apo(a), an activity mostly contained in
the Kringle V-protease region. A monoclonal antibody specific
for Kringle V inhibited the apo(a)-mediated effect on IL-8. We conclude
that Lp(a) via elements contained in the C-terminal domain of apo(a)
causes in THP-1 macrophages an increased production of IL-8, a
chemokine with pro-inflammatory properties, an event that may be
relevant to the process of atherosclerosis.
*
This work was supported by National Institutes of Health
Grants HL18577 and HL63115.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Edelstein, B. Philips, D. Pfaffinger, and A. M. Scanu The oxidized phospholipids linked to human apolipoprotein(a) do not derive from circulating low-density lipoproteins and are probably of cellular origin FASEB J, March 1, 2009; 23(3): 950 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hoover-Plow, E. Hart, Y. Gong, A. Shchurin, and T. Schneeman A Physiological Function for Apolipoprotein(a): A Natural Regulator of the Inflammatory Response Experimental Biology and Medicine, January 1, 2009; 234(1): 28 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tsimikas, L. D. Tsironis, and A. D. Tselepis New Insights Into the Role of Lipoprotein(a)-Associated Lipoprotein-Associated Phospholipase A2 in Atherosclerosis and Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2094 - 2099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Edelstein, M. Yousef, and A. M. Scanu Elements in the C terminus of apolipoprotein [a] responsible for the binding to the tenth type III module of human fibronectin J. Lipid Res., December 1, 2005; 46(12): 2673 - 2680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tsimikas, E. S. Brilakis, E. R. Miller, J. P. McConnell, R. J. Lennon, K. S. Kornman, J. L. Witztum, and P. B. Berger Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery Disease N. Engl. J. Med., July 7, 2005; 353(1): 46 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yagyu, H. Kobayashi, H. Matsuzaki, K. Wakahara, T. Kondo, N. Kurita, H. Sekino, K. Inagaki, M. Suzuki, N. Kanayama, et al. Thalidomide Inhibits Tumor Necrosis Factor-{alpha}-Induced Interleukin-8 Expression in Endometriotic Stromal Cells, Possibly through Suppression of Nuclear Factor-{kappa}B Activation J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3017 - 3021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. O'Neil, M. B. Boffa, M. A. Hancock, J. G. Pickering, and M. L. Koschinsky Stimulation of Vascular Smooth Muscle Cell Proliferation and Migration by Apolipoprotein(a) Is Dependent on Inhibition of Transforming Growth Factor-{beta} Activation and on the Presence of Kringle IV Type 9 J. Biol. Chem., December 31, 2004; 279(53): 55187 - 55195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Edelstein, D. Pfaffinger, J. Hinman, E. Miller, G. Lipkind, S. Tsimikas, C. Bergmark, G. S. Getz, J. L. Witztum, and A. M. Scanu Lysine-Phosphatidylcholine Adducts in Kringle V Impart Unique Immunological and Potential Pro-inflammatory Properties to Human Apolipoprotein(a) J. Biol. Chem., December 26, 2003; 278(52): 52841 - 52847. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |