FPR-1 is an important regulator of neutrophil recruitment and a tissue-specific driver of pulmonary fibrosis

Abstract

Conflict of interest: DKF and LAM are employees of an AstraZeneca group company and may receive AstraZeneca shares as part of their usual remuneration.

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

“…Mitochondrial formyl peptides are elevated in ARDS patients ( Dorward et al, 2017 ) and formyl peptides are known to drive neutrophils in ARDS. Formyl peptide receptors (FPRs) play an important role in the activation of neutrophils ( Yang and Hwang, 2016 ; Chen et al, 2017 ), and FPR-1 expression is elevated in lung injury and fibrosis ( Leslie et al, 2020 ). Several FPR1 antagonists were discovered previously in our lab including the clinical drug propofol ( Yang et al, 2013 ; Liu et al, 2017 ; Yang et al, 2017 ; Chen et al, 2018 ) that may have potential in the development of the treatment for COVID-19 associated ARDS.…”

The ambiguous role of FPR1 in immunity and inflammation

“…13 Finally, Fpr1 −/mice do not develop pulmonary fibrosis in response to intratracheal bleomycin challenge and failed to recruit neutrophils to the damaged lungs. 2 Adoptive transfer experiments allowed to conclude that the cell type that has to express FPR1 to cause bleomycin-induced lung fibrosis is neutrophils, underscoring the importance of this leukocyte subpopulation for disease pathogenesis. 2 Of note, more than 200 single nucleotide polymorphisms (SNPs) have been described for FPR1, and this heterogeneity could influence the functional (positive or negative) role of the gene in various diseases.…”

“…2 Adoptive transfer experiments allowed to conclude that the cell type that has to express FPR1 to cause bleomycin-induced lung fibrosis is neutrophils, underscoring the importance of this leukocyte subpopulation for disease pathogenesis. 2 Of note, more than 200 single nucleotide polymorphisms (SNPs) have been described for FPR1, and this heterogeneity could influence the functional (positive or negative) role of the gene in various diseases. In some cases, such as aggressive periodontitis 14 or exudative age-related macular degeneration and polypoidal choroidal vasculopathy 15 a functional defect of the gene constitutes a potential risk factor.…”

“…1 Among the three FPRs known in humans (FPR1, FPR2 and FPR3), most studies have focused on FPR1. 2 Their main ligands, N-formylated peptides, are either produced by invading bacteria or released from degrading mitochondrial proteins contained in dying host cells. 1 Although FPRs are expressed in various immune cells 1,3 among which neutrophils, macrophages, natural killer and dendritic cells, studies on FPR1 functions mostly focus on neutrophils, which often are the leukocytes to migrate toward the site of inflammation.…”

“…1 Although FPRs are expressed in various immune cells 1,3 among which neutrophils, macrophages, natural killer and dendritic cells, studies on FPR1 functions mostly focus on neutrophils, which often are the leukocytes to migrate toward the site of inflammation. 2 FPR1 has an ambivalent role in pathogenic processes ( Figure 1). In some diseases, FPR1 has a positive effect.…”