Rapid neutrophil adhesion to activated endothelium mediated by GMP-140

Abstract

GRANULE membrane protein-140 (GMP-140), a membrane glycoprotein of platelet^1–5 and endothelial cell^6–8 secretory granules, is rapidly redistributed to the plasma membrane during cellular activation and degranulation^1,2,6,7. Also known as PADGEM protein⁴, GMP-140 (ref. 9) is structurally related to two molecules involved in leukocyte adhesion to vascular endothelium: ELAM-1, a cytokine-inducible endothelial cell receptor for neutrophils¹⁰, and the MEL-14 lymphocyte homing receptor^11,12. 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.