Thy-1 (CD90) is an interacting partner for CD97 on activated endothelial cells.
Leukocyte recruitment in response to inflammatory signals is governed, in part, by binding to Thy-1 (CD90) on activated endothelial cells (EC). In this study, we characterized the adhesion G-protein coupled receptor CD97, present on peripheral myeloid cells, as a novel interacting partner for Thy-1. CD97 was upregulated on polymorphonuclear cells (PMNC) of patients with psoriasis. In psoriatic skin lesions, CD97(+) myeloid cells colocalized with Thy-1(+) EC of small vessels in microabscesses, suggesting an interaction between CD97 and Thy-1 that was further examined by adhesion and protein-binding assays. PMNC and cell lines stably overexpressing CD97 adhered specifically to Thy-1(+)-activated human dermal EC, Thy-1(+) CHO cells, and immobilized Thy-1 protein. Binding of the CD97(+) CHO clones correlated with their CD97 expression level. Soluble CD97 bound specifically to immobilized Thy-1 protein, as well as Thy-1(+)-activated EC and CHO cells. In all assays, cellular adhesion or protein binding was blocked partially by CD97 and Thy-1-blocking mAb. Our data suggested that CD97 interacts via its stalk with Thy-1 because mAb directed to the stalk of CD97 showed stronger blocking compared with mAb to its epidermal growth factor-like domains, and binding was calcium independent. Moreover, soluble CD97 without the stalk and soluble EMR2, containing highly homologous epidermal growth factor-like domains but a different stalk, failed to bind. In summary, binding of leukocytes to activated endothelium mediated by the interaction of CD97 with Thy-1 is involved in firm adhesion of PMNC during inflammation and may play a role in the regulation of leukocyte trafficking to inflammatory sites.
Research Laboratories, Department of Surgery, University of Leipzig, 04103 Leipzig, Germany.
Elke
E
Wandel
Anja
A
Saalbach
Doreen
D
Sittig
Carl
C
Gebhardt
Gabriela
G
Aust
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D016022:Case-Control Studies; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000276:immunology; D011565:Psoriasis / Q000276:immunology; D043562:Receptors, G-Protein-Coupled; D018800:Thy-1 Antigens / Q000378:metabolism*
C095004:ADGRE5 protein, human; D015703:Antigens, CD; D043562:Receptors, G-Protein-Coupled; D018800:Thy-1 Antigens