Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis

Abstract

The pathophysiology of extrinsic allergic alveolitis (EAA) involves oxidative lung damage as well as interstitial and alveolar inflammation. Macrophages and mast cells are inflammatory components of EAA that produce both leukotrienes (LTs) and prostaglandin D 2 (PGD 2 ). In addition, PGD 2 is also produced by the free-radical-catalysed peroxidation of arachidonic acid during oxidative stress. Urinary 8-iso prostaglandin F 2 a (8-isoPGF 2 a) and serum surfactant protein D (SP-D) are considered appropriate biomarkers of oxidative stress and interstitial lung disease activity, respectively. The present study aimed to assess the association of these biomarkers with the pathophysiology of EAA.Two cases of acute EAA caused by the inhalation of fungi spores were reported. Eight asthmatic patients and six healthy control subjects were also enrolled in the current study.The serum SP-D and urinary eicosanoid (LTE 4 , PGD 2 metabolite (9a,11bPGF 2 ), 8-isoPGF 2 a) concentrations markedly increased during the acute exacerbation phase. These concentrations decreased following corticosteroid therapy in the EAA patients. There was a significant correlation between serum SP-D and urinary 9a,11bPGF 2 concentrations in the EAA patients.In conclusion, although the present study proposes that serum surfactant protein-D and urinary eicosanoids are new biomarkers involved in the various immunological responses in extrinsic allergic alveolitis, further large-scale studies are needed to investigate the role of these compounds, not just as biomarkers, but also as biological potentiators of extrinsic allergic alveolitis.

Surfactant protein A and surfactant protein D variation in pulmonary disease

“…Serum SP-D was raised by smoking, but SP-D levels were not significantly different between controls and asthmatics (Mutti et al, 2006). A variety of small clinical studies/case studies have nevertheless indicated raised serum SP-D levels associated with allergy Saikai et al, 2002;Higashi et al, 2005;Tsushima et al, 2005;Inase et al, 2006). Despite the somewhat contradictory data regarding the relations between SP-A/SP-D levels and asthma/ allergy, mouse models, explant investigations and cell culture studies together propose essential roles for SP-A and SP-D in immune regulation involved in the pathogenesis.…”

Lipid Mediator Profiling in Pulmonary Disease

“…Similarly to allergic asthma, mast cell infiltration is prominent in acute extrinsic allergic alveolitis (EAA) and elevated urinary levels of 9 , 11 -PGF 2 have been reported in these patients [24]. In addition to interstitial and alveolar inflammation, EAA pathophysiology is also characterized by oxidative lung damage, which can be partially assessed by measuring oxidative species including the isoprostanes [24].…”

“…In addition to interstitial and alveolar inflammation, EAA pathophysiology is also characterized by oxidative lung damage, which can be partially assessed by measuring oxidative species including the isoprostanes [24].…”

“…(1); whereas the biological role of structurally analogous compounds is unclear. The distribution and synthesis of oxylipins are key targets for studies involving a range of inflammatory pathologies, not only in the respiratory tract [22][23][24][25][26], but also in nephritis [27], cardiovascular diseases [28][29][30] and cancer [31]. However, to date, there are no published studies applying largescale oxylipin profiling methods to investigate respiratory diseases in clinical settings.…”

Application of ’omics technologies to biomarker discovery in inflammatory lung diseases

“…Among oxidative markers of lung diseases, 8-iso-PGF 2a is a good candidate to study the influence of oxidative stress, because it shows strong constriction properties in smooth muscle in vitro through activation of the FP receptor [126]. Indeed, high urinary levels of 8-iso-PGF 2a have been documented in extrinsic allergic alveolitis patients [127,128].…”