Functional evidence that the HECA-452 antigen is involved in the adhesion of human neutrophils and lymphocytes to tumour necrosis factor-alpha-stimulated endothelial cells.
The migration of leucocytes into tissues is a process mediated by leucocyte endothelial interactions, in which adhesion receptors play a crucial role. Recently, it was found that 80-90% of T cells in inflammatory skin diseases were reactive to the monoclonal antibody (mAb) HECA-452+ in contrast to inflamed non-cutaneous tissues. It was suggested that the HECA-452 antigen is a homing receptor for lymphocyte migration into skin. This receptor was designated cutaneous lymphocyte-associated antigen or CLA and subsequently identified as a group of related sugar moieties. E-selectin, formerly known as ELAM-1 expressed by the endothelium has been implicated to be a counter-receptor for CLA. In this study, we investigated the adhesion of HECA-452+ leucocytes, i.e. freshly isolated neutrophils and B-cell line BV173 to tumour necrosis factor-alpha (TNF-alpha)-stimulated (E-selectin+) endothelial cells. We found that the adhesion of these cells could be inhibited significantly by mAb HECA-452, in a similar fashion to CSLEX1, a mAb specific for E-selectin ligand sialyl Lewisx. This inhibiting effect of both mAb on the adhesion of polymorphonuclear leucocytes (PMN) and BV173 could only be demonstrated when the assay was performed at 4 degrees, but not at 37 degrees. Furthermore, using immunohistochemical analysis we found that the mAb HECA-452-reactive epitope is different from that recognized by CSLEX1. The present results give direct evidence that the antigen recognized by HECA-452 is involved in the adhesion of leucocytes to endothelial cells, although this antigenic epitope is different from that reactive to CSLEX1.
De Boer
O J
OJ
Department of Dermatology, University of Amsterdam, Academisch Medisch Centrum (AMC), The Netherlands.
Horst
E
E
Pals
S T
ST
Bos
J D
JD
Das
P K
PK
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008214:Lymphocytes / Q000276:immunology*; D008562:Membrane Glycoproteins; D009504:Neutrophils / Q000276:immunology*; D012867:Skin / Q000276:immunology; D012871:Skin Diseases / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha