Pulmonary surfactant phosphatidylcholines induce immunological adaptation of alveolar macrophages

Luma da Costa Loureiro; Luana da Costa Loureiro; Edson Alves Gabriel-Junior; Fabiana Albani Zambuzi; Caroline Fontanari; Helioswilton Sales-Campos; Fabiani Gai Frantz; Lúcia Helena Faccioli; Carlos Arterio Sorgi

doi:10.1016/j.molimm.2020.04.010

Pulmonary surfactant phosphatidylcholines induce immunological adaptation of alveolar macrophages

Mol Immunol. 2020 Apr 30:122:163-172. doi: 10.1016/j.molimm.2020.04.010. Online ahead of print.

Authors

Luma da Costa Loureiro¹, Luana da Costa Loureiro¹, Edson Alves Gabriel-Junior², Fabiana Albani Zambuzi², Caroline Fontanari², Helioswilton Sales-Campos³, Fabiani Gai Frantz², Lúcia Helena Faccioli², Carlos Arterio Sorgi⁴

Affiliations

¹ Instituto de Ciências Biológicas, Programa de Pós-Graduação em Imunologia Básica e Aplicada (PPGIBA), Universidade Federal do Amazonas (UFAM), Manaus, Amazonas, Brazil; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
² Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
³ Departamento de Biociências e Tecnologia, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
⁴ Instituto de Ciências Biológicas, Programa de Pós-Graduação em Imunologia Básica e Aplicada (PPGIBA), Universidade Federal do Amazonas (UFAM), Manaus, Amazonas, Brazil; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: sorgi@fcfrp.usp.br.

PMID: 32361419
DOI: 10.1016/j.molimm.2020.04.010

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-oxo-nonanoyl)-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 E₂ (PGE₂) 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.

Keywords: Alveolar macrophage; Epigenetics; Inflammation; Phosphatidylcholine; Pulmonary surfactant; Trained immunity.