Size-based effects of anthropogenic ultrafine particles on activation of human lung macrophages

Simone Marcella; Barbara Apicella; Agnese Secondo; Francesco Palestra; Giorgia Opromolla; Renato Ciardi; Valentina Tedeschi; Anne Lise Ferrara; Carmela Russo; Maria Rosaria Galdiero; Leonardo Cristinziano; Luca Modestino; Giuseppe Spadaro; Alfonso Fiorelli; Stefania Loffredo

doi:10.1016/j.envint.2022.107395

Size-based effects of anthropogenic ultrafine particles on activation of human lung macrophages

Environ Int. 2022 Aug:166:107395. doi: 10.1016/j.envint.2022.107395. Epub 2022 Jul 7.

Authors

Affiliations

¹ Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, 80131 Naples, Italy. Electronic address: [email protected].
² Istituto di Scienze e Tecnologie per l'Energia e la Mobilità Sostenibili (STEMS)-CNR, 80125 Naples, Italy. Electronic address: [email protected].
³ Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy. Electronic address: [email protected].
⁴ Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, 80131 Naples, Italy. Electronic address: [email protected].
⁵ Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, 80131 Naples, Italy. Electronic address: [email protected].
⁶ Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, 80131 Naples, Italy. Electronic address: [email protected].
⁷ Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy. Electronic address: [email protected].
⁸ Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, 80131 Naples, Italy; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy. Electronic address: [email protected].
⁹ Istituto di Scienze e Tecnologie per l'Energia e la Mobilità Sostenibili (STEMS)-CNR, 80125 Naples, Italy. Electronic address: [email protected].
¹⁰ Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, 80131 Naples, Italy; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy. Electronic address: [email protected].
¹¹ Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, 80131 Naples, Italy. Electronic address: [email protected].
¹² Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, 80131 Naples, Italy. Electronic address: [email protected].
¹³ Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, 80131 Naples, Italy. Electronic address: [email protected].
¹⁴ Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, 80131 Naples, Italy. Electronic address: [email protected].
¹⁵ Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, WAO Center of Excellence, 80131 Naples, Italy; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy. Electronic address: [email protected].

PMID: 35839670
DOI: 10.1016/j.envint.2022.107395

Abstract

The anthropogenic particulate matter (PM), suspended air dust that can be inhaled by humans and deposited in the lungs, is one of the main pollutants in the industrialized cities atmosphere. Recent studies have shown that PM has adverse effects on respiratory diseases. These effects are mainly due to the ultrafine particles (PM0.1, PM < 100 nm), which, thanks to their PM size, are efficiently deposited in nasal, tracheobronchial, and alveolar regions. Pulmonary macrophages are a heterogeneous cell population distributed in different lung compartments, whose role in inflammatory response to injury is of particular relevance. In this study, we investigated the effect of PM0.1 on Human Lung Macrophages (HLMs) activation evaluated as proinflammatory cytokines and chemokine release, Reactive Oxygen Species (ROS) production and intracellular Ca²⁺concentration ([Ca²⁺]_i). Furthermore, PM0.1, after removal of organic fraction, was fractionated in nanoparticles both smaller (NP20) and bigger (NP100) than 20 nm by a properlydeveloped analytical protocol, allowed isolating their individual contribution. Interestingly, while PM0.1 and NP20 induced stimulatory effects on HLM cytokines release, NP100 had not effect. In particular, PM0.1 induced IL-6, IL-1β, TNF-α, but not CXCL8, release from HLMs. Moreover, PM0.1, NP20 and NP100 did not induce β-glucuronidase release, a preformed mediator contained in HLMs. The long time necessary for cytokines release (18 h) suggested that PM0.1 and NP20 could induce ex-novo production of the tested mediators. Accordingly, after 6 h of incubation, PM0.1 and NP20 induced mRNA expression of IL-6, TNF-α and IL-1β. Moreover, NP20 induced ROS production and [Ca²⁺]_i increase in a time-dependent manner, without producing cytotoxicity. Collectively, the present data highlight the main proinflammatory role of NP20 among PM fractions. This is particularly of concern because this fraction is not currently covered by legal limits as it is not easily measured at the exhausts by the available technical methodologies, suggesting that it is mandatory to search for new monitoring techniques and strategies for limiting NP20 formation.

Keywords: Air pollution; Calcium homeostasis; Chemokines; Cytokines; Lung; Macrophages; Monocyte-derived macrophages; Monocytes; Nanoparticles; PM; ROS.

MeSH terms

Air Pollutants* / adverse effects
Air Pollutants* / pharmacology
Cytokines / metabolism
Humans
Interleukin-6
Lung
Macrophages, Alveolar* / metabolism
Macrophages, Alveolar* / physiology
Particle Size
Particulate Matter* / pharmacology
Reactive Oxygen Species / metabolism
Tumor Necrosis Factor-alpha / metabolism

Substances

Air Pollutants
Cytokines
Interleukin-6
Particulate Matter
Reactive Oxygen Species
Tumor Necrosis Factor-alpha