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A A Postigo

Publications and source records attributed to A A Postigo.

23 records · Page 2Linked to original sources
PubMed1992

Increased binding of synovial T lymphocytes from rheumatoid arthritis to endothelial-leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1).

The infiltration of the synovial membrane (SM) by mononuclear cells, mostly T cells, is a typical histopathological feature associated with rheumatoid arthritis (RA). The entry of T lymphocytes into the SM is believed to be mediated by a number of molecules in the endothelium that are induced in response to a series of inflammatory mediators. In this study, we have investigated the adhesion of synovial T cells from RA patients to two endothelial ligands: endothelial-leukocyte adhesion molecule-1 (ELAM-1), the only selectin known to function as a vascular addressin for T cells, and vascular cell adhesion molecule-1 (VCAM-1), the cellular ligand of VLA-4. Our results clearly demonstrate that synovial T cells isolated from both SM and synovial fluid (SF), bearing an activated and memory phenotype, displayed an enhanced capacity to interact with these two endothelial molecules as compared with T cells from peripheral blood (PB) either of the same RA patients or healthy donors. A further enhancement of VLA-4-mediated T cell binding to VCAM-1 and fibronectin could be observed when already in vivo-activated synovial T cells were stimulated in vitro with phorbol esters, suggesting the existence of several cellular affinity levels for both very late activation-4 (VLA-4) ligands. Moreover, both PB and synovial T cells from RA patients exhibited strong proliferative responses when they were cultured with either fibronectin or VCAM-1 in combination with submitogenic doses of anti-CD3 mAb. This increased endothelial binding ability of synovial T lymphocytes together with their proliferation in response to the interaction with VCAM-1 and fibronectin may represent important mechanisms in the regulation of T cell penetration and persistence in the chronically inflamed SM of RA.

Antigens, CD↗
PubMed1991

Regulated expression and function of CD11c/CD18 integrin on human B lymphocytes. Relation between attachment to fibrinogen and triggering of proliferation through CD11c/CD18.

CD11c/CD18 (p150,95) is a beta 2 integrin expressed by myeloid, natural killer and certain lymphoid cells such as some cytotoxic T cell clones and B cell malignancies. We have studied the expression and function of CD11c on resting and activated B lymphocytes. Flow cytometry, immunoprecipitation, and mRNA analyses showed that cell activation with phorbol esters or with a variety of stimuli such as Staphylococcus aureus or anti-mu antibodies in combination with cytokines induced de novo CD11c/CD18 cell surface expression on most B cells while CD11b expression was not affected. Functional analysis of CD11c/CD18 on B cells revealed that it plays a dual role. First, CD11c/CD18 is implicated in B cell proliferation, as demonstrated by the ability of several anti-CD11c monoclonal antibodies to trigger comitogenic signals; and second, the newly expressed CD11c/CD18 mediates B cell binding to fibrinogen. Our data conclusively demonstrate the role of CD11c/CD18 on both B cell activation and adhesion processes.

Antibodies, Monoclonal↗
PubMed1991

Differential expression of VLA-4 integrin by resident and peripheral blood B lymphocytes. Acquisition of functionally active alpha 4 beta 1-fibronectin receptors upon B cell activation.

Very-late antigen (VLA)-4(CD49d/CD29) constitutes the only member of the beta 1 integrin family that plays a role in the interaction of lymphoid cells with both extracellular matrix and endothelial cells through two identified ligands: fibronectin (FN) and VCAM-1, respectively. The expression and functional activity of VLA-4 has been studied in different maturation and activation stages of B cells from several cellular compartments. Resident B lymphocytes of different lymphoid organs were almost negative for VLA-4 as detected by both immunoperoxidase staining and flow cytometry analysis. However, a high expression of both chains of this heterodimer was observed when tonsillar B cells were activated in vitro with different stimuli, such as phorbol esters or Staphylococcus aureus Cowan I (SAC). Both nonactivated and in vitro activated B cells from peripheral blood constitutively expressed high levels of this surface antigen. The induced expression of VLA-4 after activation of tonsillar B lymphocytes was accompanied by the acquisition of the capacity to bind to a 38-kDa proteolytic fragment, containing the connecting segment I domain, of FN. Interestingly, nonactivated peripheral blood B cells were unable to attach to this FN fragment, in spite of their constitutive expression of VLA-4, and only acquired this functional capacity after cell activation with phorbol esters and SAC. This FN-binding acquisition was not affected by preincubation with inhibitors of protein and RNA synthesis. These results underline that the FN-binding activity of VLA-4 is dependent on processes affecting cellular activation as described for other members of the integrin family. By contrast, VLA-4-mediated homotypic aggregation of peripheral blood B cells could be triggered by anti-alpha 4 monoclonal antibodies independently of the cell activation state.

B-Lymphocytes↗
PubMed1991

Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis.

The VLA-4 (CD49d/CD29) integrin is a cell surface receptor involved in the interaction of lymphoid cells with both extracellular matrix (ECM) and endothelial cells. We have investigated the expression and function of VLA-4 fibronectin (FN) receptors on T cells localized in the inflammed synovium of patients with rheumatoid arthritis (RA). A high proportion of T cells in both synovial membrane (SM) and synovial fluid (SF) expressed the activation antigens AIM (CD69) and gp95/85 (Ea2) as well as an increased number of VLA-4 alpha and beta 1 adhesion molecules, as compared with peripheral blood (PB) T cells from the same patients. Furthermore, the majority of these activated SF T cells were able to adhere to a 38-kD FN proteolytic fragment containing the connecting segment-1 (CS-1) specifically through VLA-4 receptors, whereas a significantly lower proportion of PB T cells displayed this capacity. Therefore, our results show that activated T cells selectively localize at sites of tissue injury in RA disease and provide evidence for the in vivo regulation of the expression and function of the VLA-4 integrin. This regulatory mechanism may enable T cells either to facilitate migration or to persist at sites of inflammation.

Adult↗