Proliferative actions of muscarinic receptors expressed in macrophages derived from normal and tumor bearing mice

Abstract

Macrophages (Mps) are essential cellular components of the innate immune system. They are released from the bone marrow as immature monocytes and after circulating in the blood stream, migrate into tissues to undergo final differentiation into resident Mps. In general terms Mps behavior in breast tumors, was described as being either for or against tumor growth. Under certain well defined circumstances Mps are able to kill cells in two ways: direct tumor cytotoxicity or antibody dependent cytotoxicity. We had previously demonstrated that peritoneal Mps from LMM3 mammary tumor bearing mice (TMps) enhanced in vivo the LMM3 induced angiogenesis, promoting tumor growth while Mps from normal BALB/c mice (NMps) did not. In this work, we demonstrate that Mps, expressing functional muscarinic acetylcholine receptors, are able to proliferate in vitro in response to the muscarinic agonist carbachol. These peritoneal cells use two distinct metabolic pathways: TMps are primed by tumor presence and they proliferate mainly by activating arginase pathway and by producing high levels of prostaglandin E(2) via M(1)-M(3) receptors activation. In NMps, carbachol stimulates M(2) receptors function, triggering protein kinase C activity and induces moderate prostaglandin E(2) liberation via M(1) receptor.

Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel

“…However, the role of muscarinic receptors in the regulation of immune cell identity and function remains poorly understood. Although a number of previous studies primarily link muscarinic signaling in immune cells to proinflammatory outcomes, including the expansion of macrophages ( 79 ), more recent studies have suggested an anti-inflammatory role. In the murine small intestine, genetic deletion of Chrm3 was associated with an up-regulation of proinflammatory T helper 1 (T H 1)/T H 17 cytokines in the absence of infection ( 80 ).…”

Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases

“…Acetylcholine has been shown to affect inflammatory cells involved in asthma and COPD, by inducing proliferation or cytokine release from these cells [Kistemaker et al 2012]. The muscarinic agonist, carbachol, can induce proliferation of rodent macrophages in vitro [De la Torre et al 2008]. Cigarette smoke extract upregulates the non-neuronal cholinergic system in bronchial epithelial cells, and increases the expression of muscarinic M2 and M3 receptors.…”

Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel

“…However, the role of muscarinic receptors in the regulation of immune cell identity and function remains poorly understood. Although a number of previous studies primarily link muscarinic signaling in immune cells to pro-inflammatory outcomes, including the expansion of macrophages (69), more recent studies have suggested an anti-inflammatory role. In the murine small intestine, genetic deletion of Chrm3 was associated with an upregulation of pro-inflammatory TH1/TH17 cytokines in the absence of infection (70).…”