Linked Life Data

9514412

Source:http://linkedlifedata.com/resource/pubmed/id/9514412

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-4-2
pubmed:abstractText
Activated resident macrophages sustain atheroma, and a high macrophage content is associated with plaque vulnerability. Factors leading to differentiation and activation of these blood-derived cells remain largely uncharacterized. We investigated the contribution of interaction with collagen type I, the predominant component of atherosclerotic matrix, to differentiation and modulation of characteristic macrophage functions, including intracellular lipid accumulation and production of the typical matrix-degrading enzyme matrix metalloproteinase (MMP)-9. When used as an adhesion substrate for human peripheral blood monocytes in vitro, collagen type I increased monocyte differentiation, assessed by analysis of CD71 expression and cell spreading. Culturing on collagen type I doubled the number of differentiated monocytes at 24 hours (44.9+/-1.4% versus 18.4+/-1.7% on uncoated dishes, P<.001, n=3 independent experiments) and was a stronger stimulus for differentiation than phorbol myristate acetate, a known inducer of monocyte differentiation. The effect of substrate on intracellular accumulation of modified lipoproteins was assessed by quantitative confocal microscopy of monocytes incubated with fluorescent acetylated LDL. The collagen type I substrate also doubled the number of macrophages containing intracellular lipid and significantly increased the individual intracellular loading. Monocytes cultured on collagen type I also released more MMP-9 than did cells plated directly on plastic. The role of monocyte spreading was further assessed by treatment with colchicine, an inhibitor of cytoskeletal function, or with genistein, a nonspecific inhibitor of tyrosine kinases, shown to participate in cell adhesion. Cell spreading was inhibited in 72.3+/-6.7% of colchicine-treated and in 62.4+/-6.4% of genistein-treated monocytes (n=3, P<.01 in both cases). The same conditions also decreased secretion of MMP-9, and genistein reduced the number of acetylated LDL-containing cells (from 286+/-7 to 184+/-8 cells/mm2 with genistein, n=3, P<.001). Data showed a strong correlation (r>.98) between monocyte spreading on collagen type I and intracellular lipid accumulation. Our results indicate that interaction with vascular matrix may play an important role in differentiation of peripheral blood monocytes into resident lipid-laden macrophages, which act as central stimulators throughout the natural history of atheroma.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1079-5642
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
432-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Extracellular matrix modulates macrophage functions characteristic to atheroma: collagen type I enhances acquisition of resident macrophage traits by human peripheral blood monocytes in vitro.
pubmed:affiliation
Emory University School of Medicine, Department of Medicine, Atlanta, Ga 30322, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't