PMID- 24043262
OWN - NLM
STAT- MEDLINE
DCOM- 20140226
LR  - 20140103
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 28
IP  - 1
DP  - 2014 Jan
TI  - Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens 
      reduces murine atherosclerosis.
PG  - 288-99
LID - 10.1096/fj.13-235911 [doi]
AB  - Atherosclerosis is a lipid-driven inflammatory disease of the vessel wall, 
      characterized by the chronic activation of macrophages. We investigated whether 
      the helminth-derived antigens [soluble egg antigens (SEAs)] could modulate 
      macrophage inflammatory responses and protect against atherosclerosis in mice. In 
      bone marrow-derived macrophages, SEAs induce anti-inflammatory macrophages, 
      typified by high levels of IL-10 and reduced secretion of proinflammatory 
      mediators. In hyperlipidemic LDLR(-/-) mice, SEA treatment reduced plaque size by 
      44%, and plaques were less advanced compared with PBS-injected littermate 
      controls. The atheroprotective effect of SEAs was found to be mainly independent 
      of cholesterol lowering and T-lymphocyte responses but instead could be 
      attributed to diminished myeloid cell activation. SEAs reduced circulating 
      neutrophils and inflammatory Ly6C(high) monocytes, and macrophages showed high 
      IL-10 production. In line with the observed systemic effects, atherosclerotic 
      lesions of SEA-treated mice showed reduced intraplaque inflammation as 
      inflammatory markers [TNF-alpha, monocyte chemotactic protein 1 (MCP-1), 
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 
      (VCAM-1), and CD68], neutrophil content, and newly recruited macrophages were 
      decreased. We show that SEA treatment protects against atherosclerosis 
      development by dampening inflammatory responses. In the future, helminth-derived 
      components may provide novel opportunities to treat chronic inflammatory 
      diseases, as they diminish systemic inflammation and reduce the activation of 
      immune cells.
FAU - Wolfs, Ine M J
AU  - Wolfs IM
AD  - 1Department of Medical Biochemistry, Rm. L01-146.2, Academic Medical Center, 
      University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. 
      m.dewinther@amc.uva.nl.
FAU - Stoger, J Lauran
AU  - Stoger JL
FAU - Goossens, Pieter
AU  - Goossens P
FAU - Pottgens, Chantal
AU  - Pottgens C
FAU - Gijbels, Marion J J
AU  - Gijbels MJ
FAU - Wijnands, Erwin
AU  - Wijnands E
FAU - van der Vorst, Emiel P C
AU  - van der Vorst EP
FAU - van Gorp, Patrick
AU  - van Gorp P
FAU - Beckers, Linda
AU  - Beckers L
FAU - Engel, David
AU  - Engel D
FAU - Biessen, Erik A L
AU  - Biessen EA
FAU - Kraal, Georg
AU  - Kraal G
FAU - van Die, Irma
AU  - van Die I
FAU - Donners, Marjo M P C
AU  - Donners MM
FAU - de Winther, Menno P J
AU  - de Winther MP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130916
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Antigens, Helminth)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, LDL)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Antigens, Helminth/*metabolism
MH  - Atherosclerosis/*metabolism/*therapy
MH  - Chemokine CCL2/metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Receptors, LDL/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - immune modulation
OT  - inflammation
OT  - monocytes
OT  - mouse
OT  - schistosome
EDAT- 2013/09/18 06:00
MHDA- 2014/02/27 06:00
CRDT- 2013/09/18 06:00
PHST- 2013/09/18 06:00 [entrez]
PHST- 2013/09/18 06:00 [pubmed]
PHST- 2014/02/27 06:00 [medline]
AID - fj.13-235911 [pii]
AID - 10.1096/fj.13-235911 [doi]
PST - ppublish
SO  - FASEB J. 2014 Jan;28(1):288-99. doi: 10.1096/fj.13-235911. Epub 2013 Sep 16.