Molecular Basis of Neuroimmune Interaction in an In Vitro Coculture Approach

Abstract

A team of researchers from Nagoya, Tokyo and Hamilton developed a unique technique for studying neuroimmune interaction with confocal laser scanning fluorescence microscopy several years ago. It relies on guiding immune and nerve cell interaction by creating an adhesive environment using an in vitro coculture dish. With their technique, they are able to study details of the mechanism of how nerve cells communicate with immune cells (mast cells and T lymphocytes) and vice versa. They showed that nerve-mast cell communication could occur in the absence of an intermediary transducing cell and that the neuropeptide substance P, operating via NK-1 receptors, was a soluble factor of this communication. In addition, recently, they showed that ATP which was released from activated mast cells mediated the activation of nerve cells. Further, with their technique, Nagoya's group was able to study details of the molecular mechanism of nerve-mast cell interaction. N-cadherin and CADM1 (

P2 receptor-mediated signaling in mast cell biology

“…Higher ATP levels (up to 100 mmol/l) are present in secretory vesicles of neurons, serotonergic granules of platelets and exocrine glands (e.g., chromaffin granules of adrenal medulla, insulin-containing granules of pancreatic β-cells, and secretory granules of mast cells) [23][24][25]. The content of these vesicles and granules is released by exocytosis induced by mechanic stimulation or specific stimuli (such as cholinergic stimulation of pancreatic acini or triggering of FcεRI by antigen/IgE cross-linking in mast cells) [23,25].…”

“…The content of these vesicles and granules is released by exocytosis induced by mechanic stimulation or specific stimuli (such as cholinergic stimulation of pancreatic acini or triggering of FcεRI by antigen/IgE cross-linking in mast cells) [23,25]. The role and fate of mast cell-derived ATP will be discussed below.…”

“…Another mechanism of ATP release is via connexin-and pannexin-regulated hemichannels, which, apart from being a building block for the gap junction and allowing the diffusion of ions across the plasma membrane, are implicated in non-vesicular ATP release [25][26][27][28]. The connexinregulated ATP release has been shown for astrocytes [26], while pannexin channels are responsible for ATP secretion from an oocyte heterologous expression system [27], from erythrocytes in response to low oxygen or to sheer stress [28], and from activated T lymphocytes upon T cell receptor stimulation [29].…”

“…4). Mast cell products (neuropeptides, cytokines (e.g., TNFα), growth factors (e.g., NGF), and arachidonic acid metabolites) could directly activate nerves [11,12,25]. Tryptase, for example, directly triggers proteinase-activated receptors on neurons [105].…”

The role of histamine in neurogenic inflammation

“…Similarly, histamine also exerts autocrine effects on mast cells as mast cells have been shown to express histamine receptors H1-4 (Tore and Tuncel, 2009). Notably, the interactions between mast cells and adjacent nerves are also accomplished by adhesion molecules such as N-cadherin or cell adhesion molecule-1, a calcium-dependent adhesion protein that can be cleaved by the metalloproteinase MT5-MMP of the peptide receptors in the dorsal root ganglion (Nakanishi and Furuno, 2008;Guillot et al, 2012). …”