Cell proliferation surface receptors

Mingari, M.C. et al., Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells, Nature, 312, 641, 1984. 

Mast cells express high-affinity IgE Fc receptors (FceRI) on their surface, contain cytoplasmic granules which are major sources of histamine and other inflammatory mediators, and are activated to release and generate these mediators by IgE-dependent and non-IgE-dependent mechanisms [1]. Disturbances either in the release of mast cell mediators or in mast cell proliferation are associated with clonal mast cell disorders including monoclonal mast cell activation syndrome (MMAS) and mastocytosis respectively, which are in turn associated with some cases of anaphylaxis [2], Molecular mechanisms have been identified which may link increased releasability of mast cell mediators and conditions leading to increased mast cell numbers [3]. Patients with mastocytosis have an increased risk to develop anaphylaxis [4, 5] and those with anaphylaxis may suffer from unrecognized mastocytosis or may display incomplete features of the disease [6-8]. 

Most of these haemopoietic growth factors are glycoproteins, displaying a molecular mass in the region of 14-24 kDa. Most are produced by more than one cell type, and several such regulators can stimulate proliferation of any one haemopoietic cell lineage. This is due to the presence of receptors for several such factors on their surface. Receptor numbers for any one growth factor are low (less than 500 per cell), and proliferation can be stimulated even when only a small proportion of these are occupied. 

Evolution has provided a masterful solution to this problem. When a microbe enters the body, its component antigens combine with only those lymphocytes whose surface receptor is complementary to the shape of those antigens. The cells that bind antigen become activated and proliferate clonally to form a large... 

B7-H4 are upregulated on the surface of DCs upon contact with Tregs [15, 16]. Although for both molecules the counter-receptor is not known, it is most likely that immunosuppressive signals will be conveyed. Functional data concerning B7-H3 and B7-H4 are still limited, since they have been described rather recently. Nevertheless, similar to other members of the B7-H family, B7-H3 has clear immunosuppressive functions, as this molecule has been shown to mediate the reduction of autoimmune EAE and addition of recombinant B7-H3 molecules to mixed leukocyte reactions suppresses T-cell proliferation in vitro [17-20]. 

Although closely related, monocytes/macrophages (MO) possess features that are distinct from DCs. Due to their limited expression of T-cell costimulatory molecules, MO are not able to prime T cells de novo, but rather stimulate effector/memory T cells by the secretion of cytokines, which support T-cell proliferation. As DCs, MO differentiate from myeloid precursors and form a heterogeneous population of antigen-presenting cells (APCs) that link the innate and adaptive immune systems. However, their ability to interact with T cells via MHC class II TCR interaction(s) as well as engagement of T-cell costimulatory receptors on their surface, makes close contact between MO and Tregs likely to occur in vivo. 

To initiate a T-cell immune response, antigen presenting cells have to display antigenic peptides com-plexed with the major histocompatibility complex (MHC) on their cell surface. The T-cell receptor of CDS cells is specific for the peptide-MHC class I complex while the CD4 cell receptor binds the peptide-MHC class II complex. This binding of the peptide-MHC II complex stimulates CD4 cell proliferation and subsequent lymphokine release. This CD4 cell response can initiate a delayed hypersensitivity reaction. However CD4 activation and the production of various lymphokines is also needed for the generation of cytotoxic T-cells and for the differentiation of plasma cells from B-lymphocytes and the antibody response by these plasma cells. For their role in also the humoral immune response CD4 cells are called T-helper cells. 

TNF-a and IL-1 are current targets of antiinflammatory drug therapy. A homotrimer of 17-kDa protein subunits whose effects include the activation of neutrophils and eosinophils, induction of COX-2, induction of proinflammatory cytokines (e.g., IL-1, IL-6), enhancement of endothelial layer permeabihty, induction of adhesion molecules by endothelial cells and leukocytes, stimulation of fibroblast proliferation, degradation of cartilage, and stimulation of bone reabsorption. Two receptors mediate these effects a 55-kDa receptor (p55) and a 75-kDa receptor (p75). Each of these receptors is found in both cell surface and soluble forms. The binding of two or three cell surface receptors to TNF-a initiates an inflammatory response. Soluble p55 also acts as a signaling receptor for inflammatory responses, whereas soluble p75 acts as an antagonist. 

Mechanism of Action Ahuman epidermal growth factor that inhibits tyrosine kinases (TK) associated with transmembrane cell surface receptors found on both normal and cancer cells. One such receptor is epidermal growth factor receptor (EGFR). Therapea-tic Effect TK activity appears to be vitally important to cell proliferation and survival. Pharmacokinetics About 60% is absorbed after PO administration bioavailability is increased by food to almost 100%. Protein binding 93%. Extensively metabolized in liver. Primarily eliminated in feces minimal excretion in urine. Half-life 36 hr. 

Mectianism of Action An immunomodulator that binds to specific membrane receptors on the cell surface, inhibiting viral replication in virus-infected cells, suppressing cell proliferation, and producing reversible decreases in leukocyte and platelet counts. Therapeutic Effect Inhibits hepatitis C virus. 

This stage involves alteration in gene expression and regulation via cell surface or cytosolic receptors. Most promoters affect gene expression via perturbation of the signal transduction pathways tyrosine kinase, steroid, or G protein linked. The result is cell proliferation. 

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