Identification of surface proteins mediating adherence of CD11/CD18-deficient lymphoblastoid cells to cultured human endothelium

• Published in: The Journal of clinical investigation Vol. 85; no. 6; pp. 2019 - 2022
• Main Authors: SCHWARTZ, B. R, WAYNER, E. A, CARLOS, T. M, OCHS, H. D, HARLAN, J. M
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.06.1990
• Subjects: Antibodies, Monoclonal - immunology; Antigens, CD - immunology; Antigens, Differentiation - deficiency; Antigens, Differentiation - immunology; Biological and medical sciences; CD11 Antigens; CD18 Antigens; Cell Adhesion; Cell Adhesion Molecules - physiology; Cells, Cultured; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Hematologic and hematopoietic diseases; Humans; Integrin beta1; Leukocyte-Adhesion Deficiency Syndrome; Lymphocytes - physiology; Medical sciences; Other diseases. Hematologic involvement in other diseases; Receptors, Very Late Antigen - immunology; Human; Cell culture; Hemopathy; Lymphoblast; Leukocyte; Adhesion
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci114668

Patients with the severe form of leukocyte adhesion deficiency syndrome do not express the CD11/CD18 adhesion complex on any of their leukocytes. Nevertheless, their lymphocytes, unlike their phagocytes, emigrate to extravascular sites of inflammation, demonstrating that surface proteins other than CD11/CD18 can mediate lymphocyte adherence to endothelium. Using a B-lymphoblastoid cell line (B-LCL) established from a CD11/CD18-deficient patient and cultured human umbilical vein endothelial cells (HEC), we investigated the CD11/CD18-independent mechanism(s) of lymphocyte adherence to endothelium. Monoclonal antibodies directed to the alpha 4 polypeptide (CD49d) and the beta 1 polypeptide (CD29) of the lymphocyte VLA-4 integrin receptor (CD49d/CD29), and to vascular cell adhesion molecule-1 (VCAM-1) on the endothelial cell significantly inhibited the adherence of the CD11/CD18-deficient B-LCL to untreated HEC and to HEC treated with recombinant human tumor necrosis factor-alpha. We suggest that the interaction of the lymphocyte receptor VLA-4 with the endothelial ligand VCAM-1 induced by cytokines at sites of inflammation or immune reaction represents a CD11/CD18-independent pathway of lymphocyte emigration.