Pulmonary surfactant phosphatidylcholines induce immunological adaptation of alveolar macrophages

Author(s)

Loureiro, Luma da Costa ^{[1, 2]} ; Loureiro, Luana da Costa ^{[1, 2]} ; Gabriel-Junior, Edson Alves ^[1] ; Zambuzi, Fabiana Albani ^[1] ; Fontanari, Caroline ^[1] ; Sales-Campos, Helioswilton ^[3] ; Frantz, Fabiani Gai ^[1] ; Faccioli, Lucia Helena ^[1] ; Sorgi, Carlos Arterio ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Ribeirao Preto, SP - Brazil

^[2] Univ Fed Amazonas UFAM, Programa Posgrad Imunol Basica & Aplicada PPGIBA, Inst Ciencias Biol, Manaus, Amazonas - Brazil

^[3] Univ Fed Goias, Inst Patol Trop & Saude Publ, Dept Biociencias & Tecnol, Goiania, Go - Brazil

• Document type: Journal article
• Source: Molecular Immunology; v. 122, p. 163-172, JUN 2020.
• Web of Science Citations: 1

Abstract

Pulmonary surfactant plays an important role in lung surface tension, defense against invading pathogens, and immune response. Furthermore, alveolar macrophages (AM) that comprise the front line of immune defense against inhaled microorganisms are covered by a layer of pulmonary fluid. Phosphatidylcholines (PCs), including unsaturated lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), are the most prevalent phospholipids in pulmonary surfactant. POPC reacts with ozone to produce 1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine (PONPC), a soluble mediator that initiates an inflammatory reaction in the lungs. However, the modulatory effects of POPC and PONPC on biology and activity of AM remain inconclusive. The exposure of AM (cell line AMJ2-C11) to POPC and PONPC was not directly related to the production of inflammatory mediators. However, AM, pre-incubated with POPC or PONPC, showed enhanced response after lipopolysaccharide (LPS) stimulation, and increased the production of nitric oxide and cytokines. This phenomenon was also observed for classical-polarized macrophages (M1). This increment on the production of inflammatory mediators was not associated with macrophage polarization, but with up-regulation of Tlr4 and Myd88 gene expression, which was in accordance with the adaptation of immune cells. This observation was confirmed by the histone acetylation epigenetic pathway. In contrast to the priming effect of POPC on AM activity, a harmful immune response, induced on incubation with PONPC, improved prostaglandin E-2 (PGE(2)) formation, resulting in diminished bacterial phagocytosis. Additionally, PONPC induced production of CXCL1/KC, which potentially mediates neutrophil recruitment and enhances tissue inflammation. These results disclosed another dynamic mechanism by which pulmonary surfactant lipids (natural or oxidized) primed macrophage activity, thus affecting lung host defense. (AU)

• FAPESP's process: 18/15066-0 - Epigenetic programming during chronic infectious diseases: tiring out and training the innate immune system
• Grantee: Fabiani Gai Frantz
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 14/07125-6 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/00658-1 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Multi-user Equipment Program