Pentameric CRP attenuates inflammatory effects of mmLDL by inhibiting mmLDL--monocyte interactions.
Previous studies have reported that C-reactive protein (CRP) interacting with low-density lipoproteins (LDL) affects macrophage activation and LDL uptake. However, the physiological relevance of CRP-LDL interaction with circulating monocytes remains elusive. Moreover, recent studies have shown that CRP exists in two isoforms with partly opposing characteristics pentameric (pCRP) and monomeric CRP (mCRP). Here we investigated the effects of CRP interacting with minimally modified low-density lipoprotein (mmLDL) interaction in regard to events involved in formation of atherosclerotic plaque. We analyzed the effect of mmLDL on human monocytes and found a substantial increase in monocyte activation as evaluated by CD11b/CD18 expression and increased monocyte adhesion under static and under shear flow conditions to human endothelial cells. Monocyte adhesion and activation was attenuated by pCRP via the prevention of mmLDL binding to monocytes. These anti-inflammatory properties of pCRP were lost when it dissociates to the monomeric form. Our results elucidate the physiological relevance of the CRP-mmLDL interaction and furthermore confirm the importance of the previously described pCRP dissociation to mCRP as a localized inflammatory "activation" mechanism.
Baker IDI Heart & Diabetes Institute, Melbourne, Victoria 8008, Australia. steffen.eisenhardt@uniklinik-freiburg.de
Steffen U
SU
Eisenhardt
Julia
J
Starke
Jan R
JR
Thiele
Andrew
A
Murphy
G
G
Björn Stark
Nicole
N
Bassler
Dmitri
D
Sviridov
Karl
K
Winkler
Karlheinz
K
Peter
D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism*; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000737:chemistry / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013997:Time Factors
D039481:CD11b Antigen; D018821:CD18 Antigens; C509295:ITGAM protein, human; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein