Persistence of Asthmatic Response after Ammonium Persulfate-Induced Occupational Asthma in Mice

Abstract

IntroductionSince persulfate salts are an important cause of occupational asthma (OA), we aimed to study the persistence of respiratory symptoms after a single exposure to ammonium persulfate (AP) in AP-sensitized mice.Material and MethodsBALB/c mice received dermal applications of AP or dimethylsulfoxide (DMSO) on days 1 and 8. On day 15, they received a single nasal instillation of AP or saline. Airway hyperresponsiveness (AHR) was assessed using methacholine provocation, while pulmonary inflammation was evaluated in bronchoalveolar lavage (BAL), and total serum immunoglobulin E (IgE), IgG1 and IgG2a were measured in blood at 1, 4, 8, 24 hours and 4, 8, 15 days after the single exposure to the causal agent. Histological studies of lungs were assessed.ResultsAP-treated mice showed a sustained increase in AHR, lasting up to 4 days after the challenge. There was a significant increase in the percentage of neutrophils 8 hours after the challenge, which persisted for 24 hours in AP-treated mice. The extent of airway inflammation was also seen in the histological analysis of the lungs from challenged mice. Slight increases in total serum IgE 4 days after the challenge were found, while IgG gradually increased further 4 to 15 days after the AP challenge in AP-sensitized mice.ConclusionsIn AP-sensitized mice, an Ig-independent response is induced after AP challenge. AHR appears immediately, but airway neutrophil inflammation appears later. This response decreases in time; at early stages only respiratory and inflammatory responses decrease, but later on immunological response decreases as well.

Persistence of respiratory and inflammatory responses after dermal sensitization to persulfate salts in a mouse model of non-atopic asthma

“…This is compatible with a Th2 immunological response, despite the unexpected increases in levels of total serum IgG2a (characteristic of a Th1 stimulation in mice) from day 60. These results are consistent with other studies carried out by our group with the same animal model and other mouse models of asthma using LMW agents [ 9 , 11 , 20 – 23 ], which suggested a mixed Th2-Th1-type immune response in sensitized mice. It has also been proposed that an increase in IgG levels may have a protective effect in this animal model [ 24 ], as the percentage of neutrophils decreased at the same time point that IgG started to increase.…”

“…A semi-quantitative scoring system was used to grade the severity and extent of inflammation, as well as bronchiolar epithelium hyperplasia on H&E stained sections. The thickness of the infiltrate in the interalveolar septa and hyperplasia was graded as follows: 0 (normal) = absence of inflammatory cells; 1 (mild) = 1–2 layers of inflammatory cells; 2 (moderate) = 3–5 layers; 3 (severe) = more than 5 layers [ 11 ].…”

Effect of anti‐IgE in occupational asthma caused by exposure to low molecular weight agents

“…In addition to studies with patients, experimental murine research on chemical‐induced asthma due to persulfate salts showed increased levels of total serum IgE . In these experimental studies, AHR, neutrophilic airway inflammation, increases in Th, Tc, and B‐lymphocytes, a mixed Th1/Th2 immune response derived from cytokine profiles in local draining lymph nodes and BAL fluid, and serum IgG1/IgG2a levels were reported after AP sensitization and challenge . Moreover, we were able to show that lymphocytes from sensitized mice could be directly triggered to proliferate by in vitro restimulation with the sensitizing agent.…”

“…AP, ammonium persulfate; BAL, bronchoalveolar lavage; CI, confidence intervals; IL, interleukin; NT, no treatment; T, treatment increases in Th, Tc, and B-lymphocytes, a mixed Th1/Th2 immune response derived from cytokine profiles in local draining lymph nodes and BAL fluid, and serum IgG1/IgG2a levels were reported after AP sensitization and challenge. 12,25 Moreover, we were able to show that lymphocytes from sensitized mice could be directly triggered to proliferate by in vitro restimulation with the sensitizing agent. These results suggest that OA due to persulfate salts may be caused by a complex interaction of an innate and a mixed Th1/Th2 adaptive immune response.…”

“…1 The presence of neutrophils is an important feature of certain types of OA, 10,22 and previously, studies have also demonstrated an increase in the total number of airway neutrophils in the mouse model of chemical-induced asthma. 12,25 Neutrophils are the first cells to migrate toward the site of inflammation during an innate immune response to tissue damage, and they have been implicated in the initiation phase (T-and B-lymphocyte activation in lymph nodes) and in the effector phase (AHR, lung inflammation, and epithelial damage). 31 To our knowledge, the present study is the first report of an OmAb effect on neutrophils.…”