Cloning of the mouse endothelial selectins. Expression of both E- and P-selectin is inducible by tumor necrosis factor alpha.
E-selectin (ELAM-1) and P-selectin (GMP-140, PADGEM, CD62) have both been described as human endothelial cell adhesion molecules for neutrophils and monocytes. Cell surface appearance of these two proteins on human umbilical vein endothelial cells can be regulated by different mechanisms: E-selectin is transcriptionally induced, within hours, by tumor necrosis factor alpha (TNF-alpha) while P-selectin is transported from storage granules to the plasma membrane within minutes upon induction by various stimulating agents. We have obtained cDNA clones covering the full-length coding sequence of the homologous mouse proteins for both endothelial selectins. We show that synthesis of mouse P-selectin, like that of E-selectin, is transiently induced by TNF-alpha in several endothelioma cell lines derived from different mouse tissues. This induction was monitored on both the RNA as well as the protein level. The TNF induced, newly synthesized P-selectin protein was detected on the cell surface. Protein expression of P-selectin increased with a slightly lower rate than expression of E-selectin. In organ cultures of lung tissue from TNF-injected mice, the synthesis of P-selectin was clearly elevated compared to control mice. The bovine P-selectin homolog recognized by cross-reaction with anti-mouse P-selectin antibodies was also TNF-inducible in primary capillary endothelial cells from adrenal cortex and in aorta-derived endothelial cells. Thus, P-selectin can be regulated on two different levels. While the transport of stored P-selectin to the cell surface is controlled by regulated secretion of storage granules, the synthesis and surface expression can be induced by TNF-alpha similarly to that of E-selectin.
Weller
A
A
Hans-Spemann-Laboratory, Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Isenmann
S
S
Vestweber
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002417:Cattle; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA; D019040:E-Selectin; D004727:Endothelium / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006390:Hemangioendothelioma / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D011233:Precipitin Tests; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA