Role of the GRO family of chemokines in monocyte adhesion to MM-LDL-stimulated endothelium.
We have previously shown that treatment of endothelial cells with minimally modified LDL (MM-LDL) induces the binding of monocytes to unknown endothelial receptor molecules. We now report that a member of the GRO family of chemokines plays a role in MM-LDL-induced monocyte binding. A cDNA library made from rabbit aortic endothelial cells (RAEC) treated with MM-LDL was expression screened for molecules inducing binding of a human monocyte cell line (THP-1). A cDNA was isolated with 75% homology to GRO. GRO mRNA levels were significantly elevated after exposure of RAEC or human aortic endothelial cells (HAEC) to MM-LDL. HAEC treated with MM-LDL displayed an increase in a surface-associated protein that bound to antibody against GRO despite low levels of GRO in the medium. Antibody to GRO significantly inhibited the binding of monocytes to MM-LDL-treated RAEC and HAEC. The increase in GRO expression and monocyte binding were reduced by incubating MM-LDL-treated endothelial cells with heparin (in a method that releases heparan sulfate bound molecules from the cell surface). These results suggest that GRO related chemokines are bound to the surface of MM-LDL-treated endothelial cells and may contribute to the monocyte adhesion induced by MM-LDL.
Department of Medicine, University of California at Los Angeles 90024.
D
D
Schwartz
A
A
Andalibi
L
L
Chaverri-Almada
J A
JA
Berliner
T
T
Kirchgessner
Z T
ZT
Fang
P
P
Tekamp-Olson
A J
AJ
Lusis
C
C
Gallegos
A M
AM
Fogelman
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006133:Growth Substances / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits
C475829:CXCL1 protein, human; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D006493:Heparin