HDL does not influence the polarization of human monocytes toward an alternative phenotype.
BACKGROUND
Macrophages are crucial cells in the pathogenesis of atherosclerosis. Macrophages are plastic cells which can switch from a classical pro-inflammatory M1 to an alternative anti-inflammatory M2 macrophage phenotype, depending on the environmental stimuli. Because high-density lipoprotein (HDL) cholesterol levels are inversely correlated to cardiovascular disease and since HDL displays anti-inflammatory properties, we investigated whether HDL can affect alternative macrophage differentiation of primary human monocytes in the presence of interleukin (IL)-4, a M2 macrophage polarization driver, in vitro and ex vivo.


RESULTS
M2 macrophages are highly responsive to HDL stimulation, since the expression of pentraxin 3 (PTX3), a well known HDL target gene, is induced by HDL more strongly in M2 macrophages than in control unpolarized resting macrophages (RM). As expected, the expression of M2 markers, such as Mannose Receptor (MR), CD200 Receptor (CD200R), Coagulation factor XIII A1 (F13A1), IL-1 receptor antagonist (IL-1RA) and IL10, was induced in IL-4 polarized M2 macrophages compared to RM. However, incubation with HDL added in vitro did not modulate the gene expression of M2 macrophage polarization markers. Moreover, monocytes isolated from subjects with genetically low HDL levels, carrying ABCA1 or LCAT mutations, differentiated ex vivo into M2 macrophages without any difference in the alternative macrophage marker expression profile.


CONCLUSIONS
These in vitro and ex vivo results indicate that, contrary to mouse macrophages, HDL does not influence macrophage M2 polarization of human monocyte-derived macrophages. Thus, the anti-inflammatory properties of HDL in humans are probably not related to the enhancement of the M2 macrophage phenotype.
Université Lille 2, F-59000 Lille, France; Inserm, U1011, F-59000 Lille, France; Institut Pasteur de Lille, F-59019 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
Sophie
S
Colin
Université Lille 2, F-59000 Lille, France; Inserm, U1011, F-59000 Lille, France; Institut Pasteur de Lille, F-59019 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
Mélanie
M
Fanchon
Université Lille 2, F-59000 Lille, France; Inserm, U1011, F-59000 Lille, France; Institut Pasteur de Lille, F-59019 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
Loic
L
Belloy
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Andrea E
AE
Bochem
Université Lille 2, F-59000 Lille, France; Inserm, U1011, F-59000 Lille, France; Institut Pasteur de Lille, F-59019 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
Corinne
C
Copin
Université Lille 2, F-59000 Lille, France; Inserm, U1011, F-59000 Lille, France; Institut Pasteur de Lille, F-59019 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
Bruno
B
Derudas
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Erik S G
ES
Stroes
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
G Kees
GK
Hovingh
University of Groningen, University Medical Center Groningen, Molecular Genetics, 9713 AV Groningen, The Netherlands.
Jan A
JA
Kuivenhoven
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Geesje M
GM
Dallinga-Thie
Université Lille 2, F-59000 Lille, France; Inserm, U1011, F-59000 Lille, France; Institut Pasteur de Lille, F-59019 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France. Electronic address: bart.staels@pasteur-lille.fr.
Bart
B
Staels
Université Lille 2, F-59000 Lille, France; Inserm, U1011, F-59000 Lille, France; Institut Pasteur de Lille, F-59019 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
Giulia
G
Chinetti-Gbaguidi
D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000276:immunology; D000328:Adult; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers; D016764:Cell Polarity / Q000276:immunology*; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000276:immunology* / Q000494:pharmacology; D005176:Factor XIII / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D064446:Orexin Receptors; D010641:Phenotype; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D055815:Young Adult
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000954:Antigens, Surface; D015415:Biomarkers; C477337:CD200R1 protein, human; D008076:Cholesterol, HDL; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; C064015:factor XIII subunit A; D005176:Factor XIII; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
Alternative polarization; HDL; Human macrophages; Inflammation