Bispecific receptor globulins, novel tools for the study of cellular interactions. Preparation and characterization of an E-selectin/P-selectin bispecific receptor globulin.
In recent years the functional consequences of receptor/ligand interactions have been studied in vitro and in vivo using monospecific recombinant immunoglobulin fusion proteins (recombinant/receptor globulins, Rg). These proteins are encoded by chimeric genes composed of a DNA fragment encoding the extracellular domain of a cell surface protein grafted onto a DNA fragment encoding immunoglobulin constant domains. In order to extend the range of applications of Rgs we investigated the possibility of preparing bispecific Rgs. These bispecific fusion proteins contain the extracellular domains of two cell surface proteins held together in close proximity by the constant domains of an immunoglobulin. Here we describe the preparation and characterization of a bispecific Rg which contains the extracellular domains of two adhesion molecules expressed by activated vascular endothelial cells, E-selectin and P-selectin. These two proteins play an important role in initiating leukocyte adhesion to the vascular cell wall at sites of inflammation. Binding studies showed that the E-selectin/P-selectin bispecific immunoglobulin fusion protein (ELAM-1/GMP140 Rg) has an enhanced ability to bind to the myeloid cell line HL60 when compared to the monospecific Rg fusion proteins from which it was derived.
Dietsch
M T
MT
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Smith
V F
VF
Cosand
W L
WL
Damle
N K
NK
Ledbetter
J A
JA
Linsley
P S
PS
Aruffo
A
A
D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000276:immunology; D002460:Cell Line / Q000276:immunology; D019040:E-Selectin; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000737:chemistry*; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry* / Q000276:immunology; D011971:Receptors, Immunologic / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins