Lawrence A Potempa - Monomeric C-reactive protein activates endothelial cells via interaction with lipid raft microdomains

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      Publication Details (including relevant citation   information):

      FASEB   J.

        23, 1806–1816 (2009)

      Abstract:

      Emerging   evidence indicates that in addition

      to native   pentameric C-reactive protein (CRP),

      monomeric   CRP (mCRP) also plays an active role in

      inflammation   associated with cardiovascular diseases.

      mCRP   activates endothelial cells, one of the critical

      events in   cardiovascular diseases; however, the underlying

      molecular   mechanisms are incompletely understood.

      Here we   report that association of mCRP with

      human aortic   and coronary artery endothelial cells is

      predominantly   due to membrane insertion rather than

      binding to   the surface proteins FcgammaRs and proteoglycans.

      We identify lipid rafts as the preferential membrane

      microdomains for mCRP anchorage. mCRP

      binding depends on membrane cholesterol content and

      is synergistically mediated by the putative cholesterol

      binding consensus sequence of CRP (aa 35–47) and the

      C-terminal   octapeptide (aa 199–206). Conversely, disrupting

      during   inflammation.

      lipid rafts   with methyl

      treatment of   rabbit thoracic aorta and carotid artery segments

      with nystatin prevented mCRP-induced IL-8

      release. Our data identify mCRP-lipid raft interaction

      as an important mechanism in mediating cellular responses

      to mCRP and lend further support to the

      notion of mCRP regulation of endothelial cell function

      cyclodextrin or nystain

      Address (URL): http://