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

DE LA TORRE EULALIA; GENARO ANA; RIBEIRO MARÍA L; PAGOTTO ROMINA; PIGNATARO OMAR P; SALES MARÍA E

BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE

Elsevier

Año: 2007

0925-4439

Abstract Macrophages (Mps) are essential cellular components of the innate immune system. They are released from the bone marrow as immaturemonocytes and after circulating in the blood stream, migrate into tissues to undergo final differentiation into resident Mps. In general terms Mpsbehavior 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 E2 via M1–M3 receptors activation. In NMps, carbachol stimulates M2 receptors function, triggering protein kinase C activity and induces moderate prostaglandin E2 liberation via M1 receptor.