Leukocyte activation by triglyceride-rich lipoproteins.
OBJECTIVE
Postprandial lipemia has been linked to atherosclerosis and inflammation. Because leukocyte activation is obligatory for atherogenesis, leukocyte activation by triglyceride-rich lipoproteins (TRLs) was investigated.


RESULTS
The expression of CD11b and CD66b after incubation with glucose and native and artificial TRLs (NTRL and ATRL) in vivo and in vitro was evaluated by flowcytometry. Oral fat loading tests showed an increased expression of CD11b on monocytes and neutrophils and CD66b on neutrophils. In 11 volunteers, postprandial leukocytes became enriched with meal-derived fatty acids ([1-(13)C]16:0) suggesting uptake of exogenous fat. ApoB binding on leukocytes measured by flowcytometry in 65 subjects was highest on neutrophils and monocytes suggesting adherence of apoB-containing lipoproteins. Physiological concentrations of TRLs showed 62% increased neutrophil CD11b and a dose-dependent increased monocyte CD11b up to 84% in vitro. Incubations with lipid emulsions in the hypertriglyceridemic range showed a 5-fold increased monocyte CD11b expression, which was higher than the positive control (fMLP), and a dose-dependent 2- to 3-fold increased neutrophil CD11b and CD66b. The oxidative scavenger DMTU decreased the neutrophil CD66b expression by 36%.


CONCLUSIONS
Acute hypertriglyceridemia is a leukocyte activator most likely by direct interaction between TRLs and leukocytes and uptake of fatty acids. TG-mediated leukocyte activation is an alternative proinflammatory and proatherogenic mechanism of hypertriglyceridemia in part associated to the generation of oxidative stress.
Alipour
Arash
A
Department of Internal Medicine, University Medical Center Utrecht, The Netherlands.
van Oostrom
Antonie J H H M
AJ
Izraeljan
Alisa
A
Verseyden
Caroline
C
Collins
Jennifer M
JM
Frayn
Keith N
KN
Plokker
Thijs W M
TW
Elte
Jan Willem F
JW
Castro Cabezas
Manuel
M
D015703:Antigens, CD / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000276:immunology; D039481:CD11b Antigen / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D005227:Fatty Acids / Q000097:blood; D058851:GPI-Linked Proteins; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000276:immunology; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications / Q000276:immunology; D066298:In Vitro Techniques; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress; D019518:Postprandial Period / Q000276:immunology / Q000502:physiology; D014280:Triglycerides / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology*
D015703:Antigens, CD; D001055:Apolipoproteins B; D039481:CD11b Antigen; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D004041:Dietary Fats; D005227:Fatty Acids; D058851:GPI-Linked Proteins; C509295:ITGAM protein, human; D014280:Triglycerides