PMID- 15286809
OWN - NLM
STAT- MEDLINE
DCOM- 20040825
LR  - 20220310
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 114
IP  - 3
DP  - 2004 Aug
TI  - IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL 
      and protects from atherosclerosis.
PG  - 427-37
AB  - During atherogenesis, LDL is oxidized, generating various oxidation-specific 
      neoepitopes, such as malondialdehyde-modified (MDA-modified) LDL (MDA-LDL) or the 
      phosphorylcholine (PC) headgroup of oxidized phospholipids (OxPLs). These 
      epitopes are recognized by both adaptive T cell-dependent (TD) and innate T 
      cell-independent type 2 (TI-2) immune responses. We previously showed that 
      immunization of mice with MDA-LDL induces a TD response and atheroprotection. In 
      addition, a PC-based immunization strategy that leads to a TI-2 expansion of 
      innate B-1 cells and secretion of T15/EO6 clonotype natural IgM antibodies, which 
      bind the PC of OxPLs within oxidized LDL (OxLDL), also reduces atherogenesis. 
      T15/EO6 antibodies inhibit OxLDL uptake by macrophages. We now report that 
      immunization with MDA-LDL, which does not contain OxPL, unexpectedly led to the 
      expansion of T15/EO6 antibodies. MDA-LDL immunization caused a preferential 
      expansion of MDA-LDL-specific Th2 cells that prominently secreted IL-5. In turn, 
      IL-5 provided noncognate stimulation to innate B-1 cells, leading to increased 
      secretion of T15/EO6 IgM. Using a bone marrow transplant model, we also 
      demonstrated that IL-5 deficiency led to decreased titers of T15/EO6 and 
      accelerated atherosclerosis. Thus, IL-5 links adaptive and natural immunity 
      specific to epitopes of OxLDL and protects from atherosclerosis, in part by 
      stimulating the expansion of atheroprotective natural IgM specific for OxLDL.
FAU - Binder, Christoph J
AU  - Binder CJ
AD  - Division of Endocrinology & Metabolism, Department of Medicine, University of 
      California, San Diego, La Jolla 92093-0682, USA.
FAU - Hartvigsen, Karsten
AU  - Hartvigsen K
FAU - Chang, Mi-Kyung
AU  - Chang MK
FAU - Miller, Marina
AU  - Miller M
FAU - Broide, David
AU  - Broide D
FAU - Palinski, Wulf
AU  - Palinski W
FAU - Curtiss, Linda K
AU  - Curtiss LK
FAU - Corr, Maripat
AU  - Corr M
FAU - Witztum, Joseph L
AU  - Witztum JL
LA  - eng
GR  - R01 HL069464/HL/NHLBI NIH HHS/United States
GR  - R01 HL057505/HL/NHLBI NIH HHS/United States
GR  - HL69464/HL/NHLBI NIH HHS/United States
GR  - R01 HL035297/HL/NHLBI NIH HHS/United States
GR  - HL56989/HL/NHLBI NIH HHS/United States
GR  - P50 HL056989/HL/NHLBI NIH HHS/United States
GR  - HL35297/HL/NHLBI NIH HHS/United States
GR  - R01 HL043815/HL/NHLBI NIH HHS/United States
GR  - HL43815/HL/NHLBI NIH HHS/United States
GR  - HL57505/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Epitopes)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Interleukin-5)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (oxidized low density lipoprotein)
RN  - 4Y8F71G49Q (Malondialdehyde)
SB  - IM
CIN - J Clin Invest. 2004 Aug;114(3):317-9. PMID: 15286796
MH  - Animals
MH  - Antibody Formation
MH  - Arteriosclerosis/*prevention & control
MH  - Bone Marrow Transplantation
MH  - Disease Models, Animal
MH  - Epitopes/*immunology
MH  - Female
MH  - *Immunity, Innate
MH  - Immunoglobulin M/metabolism
MH  - Interleukin-5/deficiency/genetics/*metabolism
MH  - Lipoproteins, LDL/drug effects/immunology/*metabolism
MH  - Malondialdehyde/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Th2 Cells/immunology
PMC - PMC484976
EDAT- 2004/08/03 05:00
MHDA- 2004/08/26 05:00
PMCR- 2004/08/01
CRDT- 2004/08/03 05:00
PHST- 2003/11/06 00:00 [received]
PHST- 2004/05/25 00:00 [accepted]
PHST- 2004/08/03 05:00 [pubmed]
PHST- 2004/08/26 05:00 [medline]
PHST- 2004/08/03 05:00 [entrez]
PHST- 2004/08/01 00:00 [pmc-release]
AID - 20479 [pii]
AID - 10.1172/JCI20479 [doi]
PST - ppublish
SO  - J Clin Invest. 2004 Aug;114(3):427-37. doi: 10.1172/JCI20479.