Jornal de doenças pulmonares e tratamento

Alveolar Macrophage Propagation is Controlled by Several Neutrophil Death Alleyway

Abstract

Xiaochen Zhang

The proliferation and self-renewal of alveolar macrophages (AM) are significant components of the microenvironment of lung tissue. The effect of immune cells, particularly neutrophils, on the homeostasis or functionality of AM is not fully understood. In this investigation, we used CXCL1 to promote neutrophil in vivo migration into bronchoalveolar lavage (BAL) fluid and lung, and we co-cultured these cells with AMs in vitro. It was discovered that BAL neutrophils (BAL-neutrophils) as opposed to BM-neutrophils limit AM growth. An analysis of data that was made accessible to the public revealed that there was significant molecular heterogeneity between blood and BM neutrophils and lung neutrophils. Unexpectedly, BAL-neutrophils from mice infected with the influenza virus PR8 (PR8-neutrophils) did not prevent the growth of AMs. Additionally, bulk RNA sequencing demonstrated that co-culturing AMs with PR8 neutrophils caused IFN- to be produced. In addition, BAL neutrophils from mice infected with PR8 altered the polarisation and phagocytosis of AMs and AMs co-cultured with BAL neutrophils had increased expression of metabolism- and ROS-associated genes. Combining inhibitors of various neutrophil death mechanisms reversed the inhibition of AM growth by BAL-neutrophils. Our findings imply that different neutrophil cell death processes control the proliferation of AMs. An alternative therapeutic approach for enhancing AM homeostasis in respiratory diseases may involve targeting neutrophil death.