An alternative leukocyte homotypic adhesion mechanism, LFA-1/ICAM-1-independent, triggered through the human VLA-4 integrin.
The VLA-4 (CD49d/CD29) integrin is the only member of the VLA family expressed by resting lymphoid cells that has been involved in cell-cell adhesive interactions. We here describe the triggering of homotypic cell aggregation of peripheral blood T lymphocytes and myelomonocytic cells by mAbs specific for certain epitopes of the human VLA alpha 4 subunit. This anti-VLA-4-induced cell adhesion is isotype and Fc independent. Similar to phorbol ester-induced homotypic adhesion, cell aggregation triggered through VLA-4 requires the presence of divalent cations, integrity of cytoskeleton and active metabolism. However, both adhesion phenomena differed at their kinetics and temperature requirements. Moreover, cell adhesion triggered through VLA-4 cannot be inhibited by cell preincubation with anti-LFA-1 alpha (CD11a), LFA-1 beta (CD18), or ICAM-1 (CD54) mAb as opposed to that mediated by phorbol esters, indicating that it is a LFA-1/ICAM-1 independent process. Antibodies specific for CD2 or LFA-3 (CD58) did not affect the VLA-4-mediated cell adhesion. The ability to inhibit this aggregation by other anti-VLA-4-specific antibodies recognizing epitopes on either the VLA alpha 4 (CD49d) or beta (CD29) chains suggests that VLA-4 is directly involved in the adhesion process. Furthermore, the simultaneous binding of a pair of aggregation-inducing mAbs specific for distinct antigenic sites on the alpha 4 chain resulted in the abrogation of cell aggregation. These results indicate that VLA-4-mediated aggregation may constitute a novel leukocyte adhesion pathway.
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
M R
MR
Campanero
R
R
Pulido
M A
MA
Ursa
M
M
Rodríguez-Moya
M O
MO
de Landázuri
F
F
Sánchez-Madrid
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion; D016029:Receptors, Very Late Antigen