Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells.

Abstract

Abstract. The tissue-specific homing of lymphocytes is directed by specialized high endothelial venules (HEV). At least three functionally independent lymphocyte/HEV recognition systems exist, controlling the extravasation of circulating lymphocytes into peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches or appendix), and the synovium of inflamed joints. We report here that antibodies capable of inhibiting human lymphocyte binding to one or more HEV types recognize a common 85-95-kD lymphocyte surface glycoprotein antigen, defined by the nonblocking monoclonal antibody, Hermes-1. We demonstrate that MEL-14, a monoclonal antibody against putative lymph node "homing receptors" in the mouse, functionally inhibits human lymphocyte binding to lymph node HEV but not to mucosal or synovial HEV, and cross-reacts with the 85-95-kD Hermes-1 antigen. Furthermore, we show that Hermes-3, a novel antibody produced by immunization with Hermes-1 antigen isolated from a mucosal HEV-specific cell line, selectively blocks lymphocyte binding to mucosal HEV. Such tissue specificity of inhibition suggests that MEL-14 and Hermes-3 block the function of specific lymphocyte recognition elements for lymph node and mucosal HEV, respectively. Recognition of synovial HEV also involves the 85-95-kD Hermes-1 antigen, in that a polyclonal antiserum produced against the isolated antigen blocks all three classes of lymphocyte-HEV interaction. From these studies, it is likely that the Hermes-l-defined 85-95-kD glycoprotein class either comprises a family of related but functionally independent receptors for HEV, or associates both physically and functionally with such receptors. The findings imply that related molecular mechanisms are involved in several functionally independent cell-cell recognition events that direct lymphocyte traffic.

Adhesion of tumour-infiltrating lymphocytes to endothelium: a phenotypic and functional analysis

“…CD44 is an abundant multifunctional cell surface molecule that was initially inferred to be a tissue-specific homing receptor (Jalkanen et al, 1987). However, because of its broad tissue distribution it may have a more general role in facilitating binding to endothelium via its ligand hyaluronate (Aruffo et al, 1990).…”

Hyaluronic acid inhibits mRNA expression of proinflammatory cytokines and cyclooxygenase‐2/prostaglandin E2 production via CD44 in interleukin‐1‐stimulated subacromial synovial fibroblasts from patients with rotator cuff disease

“…[16][17][18][19] Interaction between HA and CD44 has been demonstrated on synovial cells from patients with rheumatoid arthritis by the HA blocking assay using anti-CD44 antibody, 20 but not on SSF from patients with rotator cuff disease.…”

CD44: A Multitude of Isoforms with Diverse Functions

“…The interaction between CD44S and HEV can be blocked with mAb Hermes-3 (Jalkanen et al, 1987), which recognizes an epitope in the membrane proximal region near the insertion site for exons 1v to 10v (Goldstein et al, 1989).…”