title: Influence of chylomicron remnants on human monocyte activation in vitro.
abstract: OBJECTIVE
  Atherosclerosis is known to be an inflammatory disease and there is increasing evidence that chylomicron remnants (CMR), the lipoproteins which carry dietary fats in the blood, cause macrophage foam cell formation and inflammation. In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is increased, and clearance of CMR from blood may be delayed, however, whether CMR contribute directly to monocyte activation and subsequent egress into the arterial wall has not been established. Here, the contribution of CMR to activation of monocyte pro-inflammatory pathways was assessed using an in vitro model.
  
  
  RESULTS
  Primary human monocytes and CMR-like particles (CRLP) were used to measure several endpoints of monocyte activation. Treatment with CRLP caused rapid and prolonged generation of reactive oxygen species by monocytes. The pro-inflammatory chemokines MCP-1 and IL-8 were secreted in nanogram quantities by the cells in the absence of CRLP. IL-8 secretion was transiently increased after CRLP treatment, and CRLP maintained secretion in the presence of pharmacological inhibitors of IL-8 production. In contrast, exposure to CRLP significantly reduced MCP-1 secretion. Chemotaxis towards MCP-1 was increased in monocytes pre-exposed to CRLP and was reversed by addition of exogenous MCP-1.
  
  
  CONCLUSIONS
  Our findings indicate that CRLP activate human monocytes and augment their migration in vitro by reducing cellular MCP-1 expression. Our data support the current hypothesis that CMR contribute to the inflammatory milieu of the arterial wall in early atherosclerosis, and suggest that this may reflect direct interaction with circulating blood monocytes.
authors.affiliation: Cardiovascular Biology and Inflammation Research Group, Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
authors.forename: C
authors.initials: C
authors.lastname: Bentley
authors.forename: N
authors.initials: N
authors.lastname: Hathaway
authors.forename: J
authors.initials: J
authors.lastname: Widdows
authors.forename: F
authors.initials: F
authors.lastname: Bejta
authors.forename: C
authors.initials: C
authors.lastname: De Pascale
authors.forename: M
authors.initials: M
authors.lastname: Avella
authors.forename: C P D
authors.initials: CP
authors.lastname: Wheeler-Jones
authors.forename: K M
authors.initials: KM
authors.lastname: Botham
authors.forename: C
authors.initials: C
authors.lastname: Lawson
mesh_terms: D050197:Atherosclerosis / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D053298:Chylomicron Remnants / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053298:Chylomicron Remnants; D016209:Interleukin-8; D017382:Reactive Oxygen Species