LFA-3, CD44, and CD45: Physiologic Triggers of Human Monocyte TNF and IL-1 Release

Abstract

The monocyte-derived cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), are central regulators of the immune response, but the physiologic stimuli for their release remain largely undefined. Engagement of three monocyte glycoproteins, LFA-3, CD44, and CD45, by specific monoclonal antibodies immobilized on plastic induced TNF-alpha and IL-1 beta release. In addition, TNF-alpha was released when monocyte LFA-3 bound immobilized, purified CD2, which is its physiologic receptor. Thus, a receptor-ligand interaction that mediates cell-cell adhesion can transmit the necessary signals for the release of monokines.

The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers

“…Con A has been reported to bind to the a and b chains of the TCR, while PHA-P (the form of PHA used in this study) binds to the TCRab and also to CD2 (O'Flynn et al, 1985(O'Flynn et al, , 1986. It has been reported that simultaneous activation of CD2 and CD3 may have a synergistic effect on T-cell activtion (Holter et al, 1988;Webb et al, 1990), which would explain the greater proliferative response observed following treatment with PHA, but not Con-A or OKT3.…”

Cytokines in context.

“…Intercellular adhesion, like adhesion of cells to matrix, can also induce cytokines. Thus, binding of macrophages to tumor cells induces TNF-a (J/inicke and Mannel, 1990), and binding of human monocytes to surfaces coated with antibodies to the intercellular adhesion molecules LFA-3 or CIM4 (the latter is also an extracellular matrix receptor; see Table 1I) induces release of TNF-e~ and IL-1/3 (Webb et al, 1990). Induction of cytokines by cell-cell interactions could account for the fact that some lymphocyte responses, normally dependent on cell-cell contact, can alternatively be driven by exogenous cytokines.…”

Activation of rat macrophages by Betafectin PGG-glucan requires cross-linking of membrane receptors distinct from complement receptor three (CR3)

“…Cross-linking membrane surface receptors by a specific ligand is a common paradigm for cell activation and is thought to mimic the receptor/ligand interaction that occurs in vivo to trigger signal transduction [43,49,50]. Particulate ␤-glucans are likely to be more efficient at receptor cross-linking due to an increased density of ligands on the particle surface.…”