Abstract
Otitis media with effusion (OME), also known as secretory otitis media, is a common condition in otorhinolaryngology. The main manifestations include middle ear effusion and conductive hearing loss. Recently, increasing attention has been paid to the etiology of OME, wherein immune dysfunction is one important pathogenic mechanism. However, it is unknown whether changes in surfactant protein A (SPA) secretion affect the phagocytic activity of macrophages in the Eustachian tube, thereby altering pathogen clearance, during the pathogenesis of OME. In our study, an OME animal model was established and evaluated. Differences in SPA levels in Eustachian tube lavage fluid between the experimental and control groups were analyzed. Cell-based experiments revealed that SPA decreased the expression of CD64 and SYK and inhibited phagocytosis by RAW264.7 cells. By using flow cytometry and immunofluorescence, we confirmed that macrophage phagocytosis decreased with increasing SPA levels. Finally, we concluded that SPA affects macrophage function and plays a role in the occurrence and development of OME.
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References
Principi N, Marchisio P, Esposito S (2016) Otitis media with effusion: benefits and harms of strategies in use for treatment and prevention. Expert Rev Anti Infect Ther 14(4):415–423. https://doi.org/10.1586/14787210.2016.1150781. Epub 2016 Feb 26 PMID: 26853095
Chantzi FM, Bairamis T, Papadopoulos NG, Kafetzis DA (2005) Otitis media with effusion: an effort to understand and clarify the uncertainties. Expert Rev Anti Infect Ther 3(1):117–129. https://doi.org/10.1586/14787210.3.1.117. PMID: 15757462
Yamanaka T, Bernstein JB, Cumella J, Parker C, Ogra PL (1982) Immunologic aspects of otitis media with effusion: characteristics of lymphocyte and macrophage reactivity. J Infect Dis 145(6):804–810. https://doi.org/10.1093/infdis/145.6.804. PMID: 6979589
Gardai SJ, Xiao YQ, Dickinson M, Nick JA, Voelker DR, Greene KE, Henson PM (2003) By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 115(1):13–23. https://doi.org/10.1016/s0092-8674(03)00758-x. PMID: 14531999
Watson A, Madsen J, Clark HW. SP-A and SP-D: Dual functioning immune molecules with antiviral and immunomodulatory properties. Front Immunol. 2021 Jan 19; 11:622598. doi: https://doi.org/10.3389/fimmu.2020.622598. PMID: 33542724; PMCID: PMC7851053
Beers MF, Hamvas A, Moxley MA, Gonzales LW, Guttentag SH, Solarin KO, Longmore WJ, Nogee LM, Ballard PL (2000) Pulmonary surfactant metabolism in infants lacking surfactant protein B. Am J Respir Cell Mol Biol 22(3):380–391. https://doi.org/10.1165/ajrcmb.22.3.3645. PMID: 10696076
Mander A, Langton-Hewer S, Bernhard W, Warner JO, Postle AD (2002) Altered phospholipid composition and aggregate structure of lung surfactant is associated with impaired lung function in young children with respiratory infections. Am J Respir Cell Mol Biol 27(6):714–721. https://doi.org/10.1165/rcmb.4746. PMID: 12444031
Seymour JF, Presneill JJ (2002) Pulmonary alveolar proteinosis: progress in the first 44 years. Am J R espir Crit Care Med 166(2):215–235. https://doi.org/10.1164/rccm.2109105. PMID: 12119235
Wright JR, Youmans DC (1993) Pulmonary surfactant protein A stimulates chemotaxis of alveolar macrophage. Am J Physiol 264(4 Pt 1):L338–L344. https://doi.org/10.1152/ajplung.1993.264.4.L338. PMID: 8476070
Janssen WJ, McPhillips KA, Dickinson MG, Linderman DJ, Morimoto K, Xiao YQ, Oldham KM, Vandivier RW, Henson PM, Gardai SJ.(2008) Surfactant proteins A and D suppress alveolar macrophage phagocytosis via interaction with SIRP alpha. Am J Respir Crit Care Med 178(2):158–67. https://doi.org/10.1164/rccm.200711-1661OC. Epub 2008 Apr 17. PMID: 18420961; PMCID: PMC2453510
Abdel-Razek O, Ni L, Yang F, Wang G (2019) Innate immunity of surfactant protein A in experimental otitis media. Innate Immun 25(7):391–400
Nathan N, Taytard J, Duquesnoy P et al (2016) Surfactant protein A: a key player in lung homeostasis. Int J Biochem Cell Biol 81(Pt A):151–155
Chen Z, Zhong M, Luo Y et al (2019) Determination of rheology and surface tension of airway surface liquid: a review of clinical relevance and measurement techniques. Respir Res 20(1):274
Yu GH, Kim HB, Ko SH et al (2018) Expression of surfactant protein-A in the Haemophilus influenzae-induced otitis media in a rat model. Int J PediatrOtorhinolaryngol 112:61–66
Paananen R, Sormunen R, Glumoff V, van Eijk M, Hallman M (2001) Surfactant proteins A and D in Eustachian tube epithelium. Am J Physiol Lung Cell Mol Physiol 281(3):L660–L667. https://doi.org/10.1152/ajplung.2001.281.3.L660. PMID: 11504694
Rosenfeld RM, Shin JJ, Schwartz SR, Coggins R, Gagnon L, Hackell JM, Hoelting D, Hunter LL, Kummer AW, Payne SC, Poe DS, Veling M, Vila PM, Walsh SA, Corrigan MD (2016) Clinical practice guideline: otitis media with effusion (update). Otolaryngol Head Neck Surg 154(1 Suppl):S1–S41. https://doi.org/10.1177/0194599815623467. PMID: 26832942
Iwano T, Kinoshita T, Hamada E, Doi T, Ushiro K, Kumazawa T (1993) Otitis media with effusion and eustachian tube dysfunction in adults and children. Acta Otolaryngol Suppl 500:66–9. https://doi.org/10.3109/00016489309126183. PMID: 8452024
Garbi N, Lambrecht BN (2017) Location, function, and ontogeny of pulmonary macrophages during the steady state. Pflugers Arch 469(3–4):561–572. https://doi.org/10.1007/s00424-017-1965-3. Epub 2017 Mar 13 PMID: 28289977
Kobayashi K, Yamanaka N, Kataura A, Ohtani S, Saito T, Akino T (1992) Presence of an 80 kilodalton protein, cross-reacted with monoclonal antibodies to pulmonary surfactant protein A, in the human middle ear. Ann OtolRhinolLaryngol 101(6):491–495. https://doi.org/10.1177/000348949210100608. PMID: 1610065
Minutti CM, García-Fojeda B, Sáenz A, de Las C-E, Guillamat-Prats R, de Lorenzo A, Serrano-Mollar A, Corbí ÁL, Casals C (2016) Surfactant protein A prevents IFN-γ/IFN-γ receptor interaction and attenuates classical activation of human alveolar macrophages. J Immunol 197(2):590–598. https://doi.org/10.4049/jimmunol.1501032. Epub 2016 Jun 6 PMID: 27271568
Bakaletz LO, DeMaria TF, Lim DJ (1987) Phagocytosis and killing of bacteria by middle ear macrophages. Arch Otolaryngol Head Neck Surg 113(2):138–144. https://doi.org/10.1001/archotol.1987.01860020030007. PMID: 3492213
Koziel H, Phelps DS, Fishman JA, Armstrong MY, Richards FF, Rose RM (1998) Surfactant protein-A reduces binding and phagocytosis of pneumocystis carinii by human alveolar macrophages in vitro. Am J Respir Cell Mol Biol 18(6):834–843. https://doi.org/10.1165/ajrcmb.18.6.3059. PMID: 9618388
Park MK, Lee BD (2013) Development of animal models of otitis media. Korean J Audiol 17(1):9–12. https://doi.org/10.7874/kja.2013.17.1.9. Epub 2013 Apr 16. PMID: 24653896; PMCID: PMC3936519
Funding
This work was supported by funding from the National Natural Science Foundation of China (81970873), the Major Fundamental Research Program of the Natural Science Foundation of Shandong Province, China (ZR2021ZD40), and the Taishan Scholars Program of Shandong Province (No. ts20130913).
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Chen, T., Li, G., Liu, W. et al. Surfactant Protein A Can Affect Macrophage Phagocytosis: An Important Pathogenic Mechanism of Otitis Media with Effusion. JARO 24, 171–180 (2023). https://doi.org/10.1007/s10162-023-00893-3
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DOI: https://doi.org/10.1007/s10162-023-00893-3