Rapid neutrophil adhesion to activated endothelium mediated by GMP-140.
Granule membrane protein-140 (GMP-140), a membrane glycoprotein of platelet and endothelial cell secretory granules, is rapidly redistributed to the plasma membrane during cellular activation and degranulation. Also known as PADGEM protein, GMP-140 is structurally related to two molecules involved in leukocyte adhesion to vascular endothelium: ELAM-1, a cytokine-inducible endothelial cell receptor for neutrophils, and the MEL-14 lymphocyte homing receptor. These three proteins define a new gene family, termed selectins, each of which contains an N-terminal lectin domain, followed by an epidermal growth factor-like module, a variable number of repeating units related to those in complement-binding proteins, a transmembrane domain, and a short cytoplasmic tail. Here we demonstrate that GMP-140 can mediate leukocyte adhesion, thus establishing a functional similarity with the other selectins. Human neutrophils and promyelocytic HL-60 cells bind specifically to COS cells transfected with GMP-140 complementary DNA and to microtitre wells coated with purified GMP-140. Cell binding does not require active neutrophil metabolism but is dependent on extracellular Ca2+. Within minutes after stimulation with phorbol esters or histamine, human endothelial cells become adhesive for neutrophils; this interaction is inhibited by antibodies to GMP-140. Thus, GMP-140 expressed by activated endothelium might promote rapid neutrophil targeting to sites of acute inflammation.
St. Francis Medical Research Institute, Oklahoma City, Oklahoma.
J G
JG
Geng
M P
MP
Bevilacqua
K L
KL
Moore
T M
TM
McIntyre
S M
SM
Prescott
J M
JM
Kim
G A
GA
Bliss
G A
GA
Zimmerman
R P
RP
McEver
D000906:Antibodies / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004727:Endothelium / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D006632:Histamine; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium