Proliferative actions of muscarinic receptors expressed in macrophages derived from normal and tumor bearing mice.
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.
de la Torre
Eulalia
E
Centro de Estudios Farmacológicos y Botánicos (CEFYBO)-CONICET. Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Genaro
Ana M
AM
Ribeiro
María L
ML
Pagotto
Romina
R
Pignataro
Omar P
OP
Sales
María E
ME
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001119:Arginase / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011976:Receptors, Muscarinic / Q000378:metabolism / Q000502:physiology*
D011976:Receptors, Muscarinic; D002217:Carbachol; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D001119:Arginase