The Lutheran blood group glycoproteins, the erythroid receptors for laminin, are adhesion molecules.
The Lutheran antigens are recently characterized glycoproteins in which the extracellular region contains five immunoglobulin like domains, suggesting some recognition function. A recent abstract suggests that the Lutheran glycoproteins (Lu gps) act as erythrocyte receptors for soluble laminin (Udani, M., Jefferson, S., Daymont, C., Zen, Q., and Telen, M. J. (1996) Blood 88, Suppl. 1, 6 (abstr.)). In the present report, we provided the definitive proof of the laminin receptor function of the Lu gps by demonstrating that stably transfected cells (murine L929 and human K562 cell lines) expressing the Lu gps bound laminin in solution and acquired adhesive properties to laminin-coated plastic dishes but not to fibronectin, vitronectin, transferrin, fibrinogen, or fibrin. Furthermore, expression of either the long-tail (85 kDa) or the short-tail (78 kDa) Lu gps, which differ by the presence or the absence of the last 40 amino acids of the cytoplasmic domain, respectively, conferred to transfected cells the same laminin binding capacity. We also confirmed by flow cytometry analysis that the level of laminin binding to red cells is correlated with the level of Lu antigen expression. Indeed, Lunull cells did not bind to laminin, whereas sickle cells from most patients homozygous for hemoglobin S overexpressed Lu antigens and exhibited an increased binding to laminin, as compared with normal red cells. Laminin binding to normal and sickle red cells as well as to Lu transfected cells was totally inhibited by a soluble Lu-Fc chimeric fragment containing the extracellular domain of the Lu gps. During in vitro erythropoiesis performed by two-phase liquid cultures of human peripheral blood, the appearance of Lu antigens in late erythroid differentiation was concomitant with the laminin binding capacity of the cultured erythroblasts. Altogether, our results demonstrated that long-tail and short-tail Lu gps are adhesion molecules that bind equally well laminin and strongly suggested that these glycoproteins are the unique receptors for laminin in normal and sickle mature red cells as well as in erythroid progenitors.
El Nemer
W
W
INSERM U76, Institut National de la Transfusion Sanguine, Paris 75015, France.
Gane
P
P
Colin
Y
Y
Bony
V
V
Rahuel
C
C
Galactéros
F
F
Cartron
J P
JP
Le Van Kim
C
C
D000818:Animals; D000941:Antigens / Q000378:metabolism; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D004912:Erythrocytes / Q000378:metabolism*; D004920:Erythropoiesis; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008188:Lutheran Blood-Group System / Q000276:immunology; D051379:Mice; D011485:Protein Binding; D017474:Receptors, Laminin / Q000378:metabolism*
D000941:Antigens; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D006023:Glycoproteins; D007797:Laminin; D008188:Lutheran Blood-Group System; D017474:Receptors, Laminin