Alteration of immunophenotype of human macrophages and monocytes after exposure to cigarette smoke

Camila Oliveira Da Silva,Tatiana Victoni,Vincent Lagente,Luís Cristóvão Pôrto,Thomas Gicquel,Pascal Loyer,Yoann Daniel,Thiago Bártholo,Elise Vène

doi:10.1038/s41598-020-68753-1

Abstract

Cigarette smoke exposure (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD). Macrophages have an important role in COPD because they release pro-inflammatory and anti-inflammatory cytokines. The present study’s we investigate the functional changes in macrophages and monocytes exposed to cigarette smoke extract (CSE). Herein, using human monocyte-derived macrophages (MDMs) from healthy donors and we found that CSE was not associated with significant changes in the production of pro inflammatory cytokines by MDMs. In contrast, exposure to CSE suppressed the production of IL-6 and Gro-a/CXCL1 by LPS-stimulated-MDMs, but had an additive effect on the release of IL-8/CXCL8 and MCP1/CCL2. However, CSE exposure was associated with greater production, TARC/CCL-17 and CCL22/MDC. Moreover, MDMs displayed a lower uptake capacity after CSE exposure. We identify, for what is to our knowledge the first time that monocytes from patients with COPD produced less IL-8/CXCL8 and Gro-α/CXCL1 after LPS stimulation and produced higher levels of TARC/CCL17 and MDC/CCL-22 after IL-4 stimulation. Our present results highlighted a skewed immune response, with an imbalance in M1 vs. M2 cytokine production. In conclusion, exposure to CS has contrasting, multifaceted effects on macrophages and monocytes. Our data may provide a better understanding of the mechanisms underlying COPD.

Highlights

Cigarette smoke exposure (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD)
Given that exposure to cigarette smoke extract (CSE) appeared to have an immunosuppressive effect on some M1 cytokines and induced M2 cytokines, we investigated the effects of exposure to CSE on IL-4 stimulated monocyte-derived macrophages (MDMs)
We found that the activation of macrophages and monocytes by CS was mechanistically complex and involved both pro-inflammatory and immunosuppressive processes

Summary

Introduction

Cigarette smoke exposure (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD). Macrophages have an important role in COPD because they release pro-inflammatory and anti-inflammatory cytokines. The present study’s we investigate the functional changes in macrophages and monocytes exposed to cigarette smoke extract (CSE). Using human monocyte-derived macrophages (MDMs) from healthy donors and we found that CSE was not associated with significant changes in the production of pro inflammatory cytokines by MDMs. In contrast, exposure to CSE suppressed the production of IL-6 and Gro-a/CXCL1 by LPS-stimulatedMDMs, but had an additive effect on the release of IL-8/CXCL8 and MCP1/CCL2. It has been suggested that the microenvironment could induce polarization states Another possibility is that distinct populations of blood monocytes are attracted to inflamed tissues, where they give rise to macrophage. In different chronic diseases (such as atherosclerosis, rheumatoid arthritis and COPD); the circulating monocytes have different p henotypes[14,15,16,17]

Objectives

Methods

Results

Conclusion