Abstract
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.
MeSH Terms
Antibodies, Monoclonal/immunology
Antigens, CD/immunology
Antigens, Differentiation/deficiency,immunology
CD11 Antigens
CD18 Antigens
Cell Adhesion
Cell Adhesion Molecules/physiology
Cells, Cultured
Endothelium, Vascular/cytology,physiology
Humans
Integrin beta1
Leukocyte-Adhesion Deficiency Syndrome
Lymphocytes/physiology
Receptors, Very Late Antigen/immunology
Chemicals
Antibodies, Monoclonal
Antigens, CD
Antigens, Differentiation
CD11 Antigens
CD18 Antigens
Cell Adhesion Molecules
Integrin beta1
Receptors, Very Late Antigen
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Schwartz B R
Department of Medicine, University of Washington, Seattle 98195.
Wayner E A
Carlos T M
Ochs H D
Harlan J M
References (24)
24 references, click to expand
-
Expression of leukocyte adherence-related glycoproteins during differentiation of HL-60 promyelocytic leukemia cells.
J Immunol. 1987 Jan 15;138(2):513-9
PMID: 2947951
-
Mechanisms of lymphocyte adhesion to endothelial cells: studies using a LFA-1-deficient cell line.
Immunology. 1989 Jan;66(1):111-6
PMID: 15493272
-
T lymphocyte adhesion to endothelial cells: mechanisms demonstrated by anti-LFA-1 monoclonal antibodies.
J Immunol. 1986 Nov 1;137(9):2901-6
PMID: 2428877
-
Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes.
Nature. 1989 May 11;339(6220):152-4
PMID: 2566120
-
Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin.
J Cell Biol. 1989 Sep;109(3):1321-30
PMID: 2527858
-
Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1.
Nature. 1989 May 4;339(6219):61-4
PMID: 2497351
-
Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes.
Cell. 1989 Dec 22;59(6):1203-11
PMID: 2688898
-
The primary structure of the alpha 4 subunit of VLA-4: homology to other integrins and a possible cell-cell adhesion function.
EMBO J. 1989 May;8(5):1361-8
PMID: 2788572
-
Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins.
Annu Rev Med. 1987;38:175-94
PMID: 3555290
-
A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo.
Blood. 1987 Jan;69(1):338-40
PMID: 3539230
-
A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1.
J Immunol. 1986 Aug 15;137(4):1270-4
PMID: 3525675
-
Characterization of the cell surface heterodimer VLA-4 and related peptides.
J Biol Chem. 1987 Aug 25;262(24):11478-85
PMID: 3497921
-
Identification and characterization of two novel lymphocyte function-associated antigens, L24 and L25.
J Immunol. 1987 Mar 1;138(5):1510-4
PMID: 3492556
-
The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features.
J Infect Dis. 1985 Oct;152(4):668-89
PMID: 3900232
-
The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro.
Blood. 1985 Jul;66(1):167-78
PMID: 4005427
-
VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site.
Cell. 1990 Feb 23;60(4):577-84
PMID: 1689216
-
VLA proteins in the integrin family: structures, functions, and their role on leukocytes.
Annu Rev Immunol. 1990;8:365-400
PMID: 2188667
-
A monoclonal antibody to VLA-4 alpha-chain (CDw49d) induces homotypic lymphocyte aggregation.
J Immunol. 1990 Feb 1;144(3):777-84
PMID: 2295817
-
Absence of monoclonal-antibody-defined protein complex in boy with abnormal leucocyte function.
Lancet. 1984 Mar 10;1(8376):535-7
PMID: 6142255
-
Severe recurrent bacterial infections associated with defective adherence and chemotaxis in two patients with neutrophils deficient in a cell-associated glycoprotein.
J Pediatr. 1982 Dec;101(6):932-40
PMID: 7143170
-
An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization.
Proc Natl Acad Sci U S A. 1979 Nov;76(11):5674-8
PMID: 293671
-
Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria.
J Clin Invest. 1973 Nov;52(11):2745-56
PMID: 4355998
-
Granulocyte chemotaxis: an improved in vitro assay employing 51 Cr-labeled granulocytes.
J Immunol. 1973 Jan;110(1):233-40
PMID: 4685404
-
Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1).
J Immunol. 1986 Jul 1;137(1):245-54
PMID: 3086451