Formation of lipid corpuscles and production of eicosanoids in macrophages derived from bone marrow activated by the classic/alternative pathway, associated with tumors

• Grant number: 15/19975-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2015
• End date: September 30, 2016
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Lúcia Helena Faccioli
• Grantee: Edson Alves Gabriel Junior
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/07125-6 - New functional aspects of eicosanoids, AP.TEM

Abstract

Macrophages are extremely versatile cells. The macrophage activation pattern is induced from the presence of factors in the cellular microenvironment, polarizing them into two distinct patterns: classic activation (M1) or alternative activation (M2). M1 Macrophages are important inducers of Th1 response. They are crucial in the immune response against intracellular organisms and tumors. M2 macrophages are more heterogeneous, but generally play a role in Th2 immune response such as death and encapsulation extracellular parasites, inhibiting inflammation of Th1 and promoting tissue repair and remodeling. M2 have also played role in immunoregulation and promotes tumor progression. Macrophages M1 and M2 are not only different in their function but also by the different expressions of receptors and enzymes related to metabolism. The lipid mediators produced by macrophages and act effectively upon activation of the innate immune response are originating from arachidonic acid (AA), which is an 20 carbon fatty acid, the precursor of eicosanoids. Tumor macrophages associated (TAMs), has been the subject of attention for being somewhat related to the destruction of tumor cells locally. Rather, its function is curiously given in favor of tumor development. Among the tumorigenic effects related to increased levels of prostaglandins in tissues include: stimulation of mitogenesis, cell growth, stimulation of angiogenesis, and apoptosis resistance. Thus, understanding the TAMs phenotype and the correlation with the eicosanoid metabolism can lead to interventions targeted antitumor.