Vascular cell adhesion molecule-1-mediated matrix metalloproteinase-2 induction in peripheral blood T cells is up-regulated in patients with HTLV-I-associated myelopathy

The expression and function of a new cytokine-induced endothelial cell adhesion protein, vascular cell adhesion molecule-1 (VCAM-1), was characterized in vitro by using a monoclonal antibody, MoAb 4B9, which recognizes a functional epitope on this protein. As determined by enzyme-linked immunosorbent assay and radioimmunoprecipitation of metabolically labeled cells, VCAM-1 was minimally expressed on unstimulated human umbilical vein endothelium (HUVE), but was rapidly induced by recombinant human tumor necrosis factor-alpha (rhTNF-alpha), rh interleukin-1, and lipopolysaccharide. In contrast to intercellular adhesion molecule-1, VCAM-1 was not induced on dermal fibroblasts or arterial smooth muscle cells after stimulation with rhTNF, or on keratinocytes after stimulation with rh interferon-gamma. MoAb 4B9 significantly inhibited the adherence of peripheral blood lymphocytes (PBL) and lymphocytic cell lines, but not neutrophils, to rhTNF- activated HUVE. The inhibitory effect of MoAb 4B9 on PBL adherence to HUVE was additive to that produced by the CD18 MoAb 60.3. These results show that VCAM-1 mediates a CD18-independent pathway of peripheral blood lymphocyte adherence to cytokine-stimulated HUVE. We propose that lymphocyte binding to VCAM-1, induced on endothelium by cytokines, may be an important component of lymphocyte emigration at sites of inflammation or immune reaction.

Download Full-text

Airway recruitment of leukocytes in mice is dependent on alpha4-integrins and vascular cell adhesion molecule-1

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.272.2.l219 ◽

1997 ◽

Vol 272 (2) ◽

pp. L219-L229 ◽

Cited By ~ 19

Author(s):

J. E. Chin ◽

C. A. Hatfield ◽

G. E. Winterrowd ◽

J. R. Brashler ◽

S. L. Vonderfecht ◽

...

Keyword(s):

T Cells ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Pulmonary Inflammation ◽

Vascular Cell Adhesion ◽

Vascular Cell ◽

Vascular Cell Adhesion Molecule ◽

Cell Adhesion Molecule 1

The involvement of the alpha4-integrin very late activation antigen 4 and vascular cell adhesion molecule-1 (VCAM-1) in leukocyte trafficking into the airways of ovalbumin (OA)-sensitized and OA-challenged mice was investigated using in vivo administration of anti-alpha4 monoclonal antibodies (mAb) PS/2, R1-2, and M/K-2.7 (MK2), specific for VCAM-1. VCAM-1 was upregulated on endothelial cells in lung tissue after OA inhalation. PS/2, R1-2, or MK2 significantly inhibited the recruitment of eosinophils and lymphocytes into the bronchoalveolar lavage (BAL) fluid and decreased inflammation in the lung tissues. Escalating in vivo doses of PS/2 or MK2 increased circulating levels of rat immunoglobulin G in the plasma. The binding of phycoerytherin-labeled anti-alpha4 mAb to blood T cells from PS/2-treated mice was reduced, implying that alpha4 sites were already occupied. T cells and eosinophils in BAL fluid from mice treated with PS/2 or MK2 were phenotypically different from controls. Selective decreases of alpha4+ T cells in the BAL fluid after PS/2 or MK2 treatment were coupled with changes in CD8+, CD11a, and CD62L expression. The alpha4-integrin and VCAM-1 may have important roles in the antigen-induced recruitment of T cells and eosinophils during OA-induced airway inflammation. The data suggest that these adhesion molecules may be suitable targets for therapeutic intervention in certain conditions of pulmonary inflammation.

Download Full-text

Effects of the very late adhesion molecule 4 antagonist WAY103 on human peripheral blood eosinophil vascular cell adhesion molecule 1–dependent functions

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2005.07.003 ◽

2005 ◽

Vol 116 (4) ◽

pp. 812-819 ◽

Cited By ~ 12

Author(s):

Julie B. Sedgwick ◽

Kristyn J. Jansen ◽

Jeffrey D. Kennedy ◽

Hirohito Kita ◽

William W. Busse

Keyword(s):

Cell Adhesion ◽

Adhesion Molecule ◽

Peripheral Blood ◽

Cell Adhesion Molecule ◽

Human Peripheral Blood ◽

Blood Eosinophil ◽

Vascular Cell Adhesion ◽

Vascular Cell ◽

Peripheral Blood Eosinophil ◽

Cell Adhesion Molecule 1

Download Full-text

Costimulation via Vascular Cell Adhesion Molecule-1 Induces in T Cells Increased Responsiveness to the CD28 Counter-receptor B7

Cellular Immunology ◽

10.1006/cimm.1993.1097 ◽

1993 ◽

Vol 148 (1) ◽

pp. 144-156 ◽

Cited By ~ 21

Author(s):

Nitin K. Damle ◽

Kerry Klussman ◽

Gina Leytze ◽

Hans D. Ochs ◽

Alejandro Aruffo ◽

...

Keyword(s):

T Cells ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Vascular Cell Adhesion ◽

Vascular Cell ◽

Vascular Cell Adhesion Molecule ◽

Cell Adhesion Molecule 1

Download Full-text

Loss of Kindlin-3 in LAD-III eliminates LFA-1 but not VLA-4 adhesiveness developed under shear flow conditions

Blood ◽

10.1182/blood-2009-04-218636 ◽

2009 ◽

Vol 114 (11) ◽

pp. 2344-2353 ◽

Cited By ~ 59

Author(s):

Eugenia Manevich-Mendelson ◽

Sara W. Feigelson ◽

Ronit Pasvolsky ◽

Memet Aker ◽

Valentin Grabovsky ◽

...

Keyword(s):

T Cells ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Human Lymphocytes ◽

Effector T Cells ◽

Vascular Cell Adhesion ◽

Vascular Cell ◽

Vascular Cell Adhesion Molecule ◽

Cell Adhesion Molecule 1

Abstract Leukocyte adhesion deficiency (LAD)–III is associated with homozygous stop codon mutations in Kindlin-3, the hematopoietic member of the Kindlin family of integrin coactivators. In addition, a subgroup of LAD-III patients has a homozygous splice junction mutation in and reduced expression of the Rap-1 guanine nucleotide exchange factor, CalDAG-GEFI (CDGI). In this study, we compared the adhesive properties of the leukocyte function-associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrins in both primary and activated leukocytes derived from these 2 LAD-III subgroups. Primary lymphocytes lacking both Kindlin-3 and CDGI lost all firm T-cell receptor–stimulated LFA-1 adhesiveness, in contrast to LAD-III lymphocytes deficient in Kindlin-3 alone. Effector T cells expanded from all tested LAD-III variants expressed normal CDGI, but lacked Kindlin-3. These Kindlin-3–null effector T cells exhibited total loss of inside-out LFA-1 activation by chemokine signals as well as abrogated intrinsic LFA-1 adhesiveness. Surprisingly, VLA-4 in Kindlin-3–null resting or effector lymphocytes retained intrinsic rolling adhesions to vascular cell adhesion molecule-1 and exhibited only partial defects in chemokine-stimulated adhesiveness to vascular cell adhesion molecule-1. Deletion of the putative β1 Kindlin-3 binding site also retained VLA-4 adhesiveness. Thus, our study provides the first evidence that Kindlin-3 is more critical to LFA-1 than to VLA-4–adhesive functions in human lymphocytes.

Download Full-text

Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells [published erratum appears in Blood 1990 Dec 1;76(11):2420]

Blood ◽

10.1182/blood.v76.5.965.965 ◽

1990 ◽

Vol 76 (5) ◽

pp. 965-970 ◽

Cited By ~ 312

Author(s):

TM Carlos ◽

BR Schwartz ◽

NL Kovach ◽

E Yee ◽

M Rosa ◽

...

Keyword(s):

Cell Adhesion ◽

Adhesion Molecule ◽

Peripheral Blood ◽

Cell Adhesion Molecule ◽

Dermal Fibroblasts ◽

Enzyme Linked Immunosorbent Assay ◽

Vascular Cell Adhesion ◽

Vascular Cell ◽

Vascular Cell Adhesion Molecule ◽

Cell Adhesion Molecule 1

Abstract The expression and function of a new cytokine-induced endothelial cell adhesion protein, vascular cell adhesion molecule-1 (VCAM-1), was characterized in vitro by using a monoclonal antibody, MoAb 4B9, which recognizes a functional epitope on this protein. As determined by enzyme-linked immunosorbent assay and radioimmunoprecipitation of metabolically labeled cells, VCAM-1 was minimally expressed on unstimulated human umbilical vein endothelium (HUVE), but was rapidly induced by recombinant human tumor necrosis factor-alpha (rhTNF-alpha), rh interleukin-1, and lipopolysaccharide. In contrast to intercellular adhesion molecule-1, VCAM-1 was not induced on dermal fibroblasts or arterial smooth muscle cells after stimulation with rhTNF, or on keratinocytes after stimulation with rh interferon-gamma. MoAb 4B9 significantly inhibited the adherence of peripheral blood lymphocytes (PBL) and lymphocytic cell lines, but not neutrophils, to rhTNF- activated HUVE. The inhibitory effect of MoAb 4B9 on PBL adherence to HUVE was additive to that produced by the CD18 MoAb 60.3. These results show that VCAM-1 mediates a CD18-independent pathway of peripheral blood lymphocyte adherence to cytokine-stimulated HUVE. We propose that lymphocyte binding to VCAM-1, induced on endothelium by cytokines, may be an important component of lymphocyte emigration at sites of inflammation or immune reaction.

Download Full-text