Production of H₂O₂ by Alveolar Macrophages in Experimental Allergic Alveolitis

Abstract

Experimental extrinsic allergic alveolitis (EAA) was induced in guinea pigs with Saccharopolyspora rectivirgula. Bronchoalveolar lavages were performed before inducing EAA (day 1, BAL 1), on day 23 (BAL 2), and on day 48 (BAL 3). The number of cells/ml in lavage fluid was increased at BAL 2 (4.79 × 106) and BAL 3 (4.29 × 106) compared with BAL 1 (0.56 × 106). The number of major cell types increased simultaneously, neutrophil becoming the predominant cell type over alveolar macrophages (AM). The production of H2O2 by AM was measured at the different phases of EAA. Adherent AM were either non‐stimulated or triggered with phorbol myristate acetate (PMA), zymosan, S. rectivirgula opsonized with normal guinea pig serum (SRNS), or S. rectivirgula opsonized with guinea pig anti‐S. rectivirgula serum (SRAS). Stimulated AM produced larger quantities of H2O2 than unstimulated cells, PMA being the most potent stimulus. At day 1, AM stimulated with S. rectivirgula and zymosan produced similar quantities of H2O2. After the induction of the disease, AM stimulated with S. rectivirgula produced larger quantities of H2O2 than with zymosan. Production of H2O2 by AM stimulated with S. rectivirgula or PMA, respectively, stayed the same at day 1 and 23, but increased sharply for both stimuli at day 48. There was no difference between H2O2 production by AM triggered with SRNS or with SRAS. This study shows that: 1) H2O2 production is enhanced, especially by the offending agent, in the course of the disease; 2) the enhanced production of H2O2 by AM is preceded by the development of alveolitis; and, 3) the opsonization with specific antibodies does not enhance the avidity of AM for the antigen.

Liposomal dexamethasone effectiveness in the treatment of hypersensitivity pneumonitis in mice

“…The importance of alveolar macrophages in this model is based on the observation that cell mediators, including TNFa and ILI as well as eicosanoids, are increased in the bronchoalveolar lavage fluid or in cultured alveolar macrophage supernatants [6,7]. Hydrogen peroxide production by alveolar macrophages from guinea pigs challenged with the same antigen is also increased [8]. Corticosteroids are known to affect the production of these mediators by macrophages [9,10,1 I].…”

Hypersensitivity pneumonitis

“…In HP this destructive and pro-inflammatory enzyme, which contributes to the break down of elastic fibres could promote the emphysema that has been observed in the chronic form of the disease (46). With activated macrophages, the influx of neutrophils plays a role in the production of oxygen-free radicals, which cause tissue damages and trigger the development of fibrosis also a hallmark of chronic HP (46,92).…”

Machine learning-based metabolism-related genes signature, single-cell RNA sequencing, and experimental validation in hypersensitivity pneumonitis

“…[ 31 ] In addition, an increase in H 2 O 2 production by macrophages was observed in a guinea pig model of exogenous HP. [ 32 ] Therefore, GPX3 could confer protection to patients with HP.…”