LRP: a new adhesion molecule for endothelial and smooth muscle cells.
We recently generated a monoclonal antibody that disrupted the association of endothelial cells with their target location during kidney development. Here, we purified the antigen of this monoclonal antibody to homogeneity using rat mesangial cell cytosol. Sequence revealed that it is a previously identified protein, termed the "laminin receptor precursor" (LRP). We found that this protein is expressed in most tissues, but immunocytochemistry revealed that it is present largely or entirely in blood vessels where it is located underneath endothelial cells and in between smooth muscle cells of the vascular wall. Vascular smooth muscle cells such as mesangial cells produce and secrete LRP into their extracellular matrix where it is present in several molecular weight forms. Endothelial cells produce very little if any of the protein, but they bind avidly to LRP-coated dishes. Anti-LRP antibodies prevent the binding of smooth muscle cells to uncoated plates, implying that cells that secrete it use it for attachment. In an assay for heterologous cell-to-cell interaction, antibodies to LRP inhibited the binding of smooth muscle cells to endothelial cells. Maturation and differentiation of blood vessels require interaction between endothelial and smooth muscle cells. LRP is a new component of the mesangial matrix, and we propose that it is an adhesion molecule that mediates an interaction between smooth muscle cells and endothelia.
Hu
C
C
Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons of Columbia University, 630 W. 168 St., New York, NY 10032, USA.
Oliver
J A
JA
Goldberg
M R
MR
Al-Awqati
Q
Q
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001485:Basement Membrane / Q000737:chemistry / Q000166:cytology; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology; D005920:Glomerular Mesangium / Q000098:blood supply / Q000737:chemistry* / Q000166:cytology*; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D011498:Protein Precursors / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D051381:Rats; D017474:Receptors, Laminin
D000911:Antibodies, Monoclonal; D011498:Protein Precursors; D017474:Receptors, Laminin