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Home / Equine Research Bank / Front Vet Sci / Salivary Scavenger and Agglutinin (SALSA) Is Expressed in Mu...
Frontiers in veterinary science2019; 6; 418; doi: 10.3389/fvets.2019.00418

Salivary Scavenger and Agglutinin (SALSA) Is Expressed in Mucosal Epithelial Cells and Decreased in Bronchial Epithelium of Asthmatic Horses.

Abstract: The Salivary Scavenger and Agglutinin (SALSA) protein is an innate immune protein with various alleged functions, including the regulation of inflammation and tissue remodeling. Transcriptomic studies of severe equine asthma (SEA) showed downregulation of the gene encoding SALSA in bronchial epithelium of asthmatic compared to non-asthmatic horses. This study aimed to characterize expression of SALSA in equine tissues by immunohistochemistry (IHC), corroborate potential differences in epithelial gene expression between asthmatic and non-asthmatic horses, and assess the structure of equine SALSA. An antibody against SALSA was validated through immunoprecipitation followed by mass spectrometry and Western blotting to recognize the equine protein. This antibody was applied to tissue microarrays (TMAs) containing 22 tissues each from four horses. A quantitative PCR assay was designed to compare gene expression for SALSA between six asthmatic and six non-asthmatic horses, before and after an asthmatic challenge, using cDNA from endoscopic bronchial biopsies as source material. The gene from bronchial cDNA samples of 10 horses, was amplified and sequenced, and translated to characterize the protein structure. Immunostaining for SALSA was detected in the mucosal surfaces of the trachea, bronchi, bronchioles, stomach, small intestine and bladder, in pancreatic and salivary gland ducts, and in uterine gland epithelium. Staining was strongest in the duodenum, and the intercalated ducts and Demilune cells of the salivary gland. SALSA was concentrated in the apical regions of the epithelial cell cytoplasm, suggestive of a secreted protein. Gene expression was significantly lower ( = 0.031) in asthmatic compared to non-asthmatic horses. Equine SALSA consisted of three to five scavenger receptor cysteine-rich (SRCR) domains, two CUB (C1r/C1s, uegf, bmp-1) domains and one Zona Pellucida domain. These domains mediate the binding of ligands involved in innate immunity. Varying numbers of SRCR domains were identified in different horses, indicating different isoforms. In summary, equine SALSA has a predilection for mucosal sites, has multiple isoforms, and has decreased expression in asthmatic horses, suggesting alterations in innate immunity in equine asthma.
Copyright © 2019 Lee, Tessier and Bienzle.
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Publication Date: 2019-11-29 PubMed ID: 31850379PubMed Central: PMC6896824DOI: 10.3389/fvets.2019.00418Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research paper is about a study on the Salivary Scavenger and Agglutinin (SALSA) protein and its decreased expression in the bronchial epithelium of asthmatic horses, pointing at potential alterations in the innate immunity of equine asthma.

Study Aim and Methodology

  • The primary aim of this study was to examine the expression of SALSA in horse tissues, validate any differences in the gene expression between asthmatic and non-asthmatic horses, and assess the structure of equine SALSA.
  • The study approach involved transcriptomic studies on severe equine asthma (SEA) and immunohistochemistry (IHC).
  • An antibody was validated against SALSA through methods such as immunoprecipitation, mass spectrometry, and Western blotting to recognize the equine protein.
  • Tissue microarrays containing tissues from four different horses were employed and gene expression for SALSA was compared between six asthmatic and six non-asthmatic horses, before and after an asthmatic challenge.
  • The researchers designed a quantitative PCR assay using cDNA from endoscopic bronchial biopsies as source material
  • The bronchial cDNA samples from 10 horses were sequenced and translated to characterize the protein structure.

Findings and Conclusion

  • Immunostaining for SALSA was observed at mucosal surfaces, in pancreatic and salivary gland ducts, and in uterine gland epithelium. The staining was most strong in the duodenum and Demilune cells of the salivary gland.
  • SALSA was majorly located in the apical regions of the epithelial cell cytoplasm pointing to its being a secreted protein.
  • A significant decrease in SALSA gene expression was identified in asthmatic horses compared to non-asthmatic horses, highlighting potential changes in the innate immunity of asthmatic horses.
  • The structure of equine SALSA consisted of three to five scavenger receptor cysteine-rich domains, two CUB domains, and one Zona Pellucida domain. These domains have the role of binding ligands that participate in innate immunity.
  • Different isoforms of horse SALSA were identified, each having a different number of SRCR domains.
  • The study concluded that equine SALSA has a preference for mucosal sites, exists in multiple isoforms, and its decreased expression could be suggesting changes in innate immunity in equine asthma.

Cite This Article

APA
Lee GKC, Tessier L, Bienzle D. (2019). Salivary Scavenger and Agglutinin (SALSA) Is Expressed in Mucosal Epithelial Cells and Decreased in Bronchial Epithelium of Asthmatic Horses. Front Vet Sci, 6, 418. https://doi.org/10.3389/fvets.2019.00418

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 6
Pages: 418
PII: 418

Researcher Affiliations

Lee, Gary Kwok Cheong
  • Department of Pathobiology, University of Guelph, Guelph, ON, Canada.
Tessier, Laurence
  • Department of Pathobiology, University of Guelph, Guelph, ON, Canada.
Bienzle, Dorothee
  • Department of Pathobiology, University of Guelph, Guelph, ON, Canada.

References

This article includes 43 references
  1. Reichhardt MP, Meri S. SALSA: A Regulator of the Early Steps of Complement Activation on Mucosal Surfaces.. Front Immunol 2016;7:85.
    doi: 10.3389/fimmu.2016.00085pmc: PMC4781872pubmed: 27014265google scholar: lookup
  2. Reichhardt MP, Holmskov U, Meri S. SALSA-A dance on a slippery floor with changing partners.. Mol Immunol 2017 Sep;89:100-110.
    doi: 10.1016/j.molimm.2017.05.029pubmed: 28668353google scholar: lookup
  3. Reichhardt MP, Loimaranta V, Thiel S, Finne J, Meri S, Jarva H. The salivary scavenger and agglutinin binds MBL and regulates the lectin pathway of complement in solution and on surfaces.. Front Immunol 2012;3:205.
    doi: 10.3389/fimmu.2012.00205pmc: PMC3397308pubmed: 22811680google scholar: lookup
  4. Holmskov U, Lawson P, Teisner B, Tornoe I, Willis AC, Morgan C, Koch C, Reid KB. Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule.. J Biol Chem 1997 May 23;272(21):13743-9.
    doi: 10.1074/jbc.272.21.13743pubmed: 9153228google scholar: lookup
  5. Ligtenberg AJ, Bikker FJ, De Blieck-Hogervorst JM, Veerman EC, Nieuw Amerongen AV. Binding of salivary agglutinin to IgA.. Biochem J 2004 Oct 1;383(Pt 1):159-64.
    doi: 10.1042/BJ20040265pmc: PMC1134054pubmed: 15228387google scholar: lookup
  6. Ligtenberg AJ, Karlsson NG, Veerman EC. Deleted in malignant brain tumors-1 protein (DMBT1): a pattern recognition receptor with multiple binding sites.. Int J Mol Sci 2010;11(12):5212-33.
    doi: 10.3390/ijms1112521pmc: PMC3100851pubmed: 21614203google scholar: lookup
  7. Jovine L, Qi H, Williams Z, Litscher E, Wassarman PM. The ZP domain is a conserved module for polymerization of extracellular proteins.. Nat Cell Biol 2002 Jun;4(6):457-61.
    doi: 10.1038/ncb802pubmed: 12021773google scholar: lookup
  8. Purushotham S, Deivanayagam C. The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs.. J Biol Chem 2014 Aug 8;289(32):21877-87.
    doi: 10.1074/jbc.M114.565507pmc: PMC4139206pubmed: 24923446google scholar: lookup
  9. Mollenhauer J, Müller H, Kollender G, Lyer S, Diedrichs L, Helmke B, Holmskov U, Ligtenberg T, Herbertz S, Krebs I, Madsen J, Bikker F, Schmitt L, Wiemann S, Scheurlen W, Otto HF, von Deimling A, Poustka A. The SRCR/SID region of DMBT1 defines a complex multi-allele system representing the major basis for its variability in cancer.. Genes Chromosomes Cancer 2002 Nov;35(3):242-55.
    doi: 10.1002/gcc.10115pubmed: 12353266google scholar: lookup
  10. Madsen J, Sorensen GL, Nielsen O, Tornøe I, Thim L, Fenger C, Mollenhauer J, Holmskov U. A variant form of the human deleted in malignant brain tumor 1 (DMBT1) gene shows increased expression in inflammatory bowel diseases and interacts with dimeric trefoil factor 3 (TFF3).. PLoS One 2013;8(5):e64441.
    doi: 10.1371/journal.pone.0064441pmc: PMC3654909pubmed: 23691218google scholar: lookup
  11. Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma.. BMC Genomics 2017 Sep 8;18(1):708.
    doi: 10.1186/s12864-017-4107-6pmc: PMC5591550pubmed: 28886691google scholar: lookup
  12. Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. Gene set enrichment analysis of the bronchial epithelium implicates contribution of cell cycle and tissue repair processes in equine asthma.. Sci Rep 2018 Nov 6;8(1):16408.
    doi: 10.1038/s41598-018-34636-9pmc: PMC6219531pubmed: 30401798google scholar: lookup
  13. Searle BC. Scaffold: a bioinformatic tool for validating MS/MS-based proteomic studies.. Proteomics 2010 Mar;10(6):1265-9.
    doi: 10.1002/pmic.200900437pubmed: 20077414google scholar: lookup
  14. Allred DC, Clark GM, Elledge R, Fuqua SA, Brown RW, Chamness GC, Osborne CK, McGuire WL. Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer.. J Natl Cancer Inst 1993 Feb 3;85(3):200-6.
    doi: 10.1093/jnci/85.3.200pubmed: 8423624google scholar: lookup
  15. Asadian P, Finnie G, Bienzle D. The expression profile of sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) in feline tissues.. Vet Immunol Immunopathol 2018 Jan;195:7-18.
    doi: 10.1016/j.vetimm.2017.11.003pubmed: 29249320google scholar: lookup
  16. Azarpeykan S, Dittmer KE. Evaluation of housekeeping genes for quantitative gene expression analysis in the equine kidney.. J Equine Sci 2016;27(4):165-168.
    doi: 10.1294/jes.27.165pmc: PMC5155135pubmed: 27974876google scholar: lookup
  17. Nazari F, Parham A, Maleki AF. GAPDH, β-actin and β2-microglobulin, as three common reference genes, are not reliable for gene expression studies in equine adipose- and marrow-derived mesenchymal stem cells.. J Anim Sci Technol 2015;57:18.
    doi: 10.1186/s40781-015-0050-8pmc: PMC4540241pubmed: 26290738google scholar: lookup
  18. Andersen CL, Jensen JL, Ørntoft TF. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets.. Cancer Res 2004 Aug 1;64(15):5245-50.
    doi: 10.1158/0008-5472.CAN-04-0496pubmed: 15289330google scholar: lookup
  19. Chow S-C, Shao J, Wang H. Sample Size Calculations in Clinical Research. 2nd Edn. Boca Raton, FL: Chapman & Hall; CRC Press.
  20. Ambruosi B, Accogli G, Douet C, Canepa S, Pascal G, Monget P, Moros Nicolás C, Holmskov U, Mollenhauer J, Robbe-Masselot C, Vidal O, Desantis S, Goudet G. Deleted in malignant brain tumor 1 is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species.. Reproduction 2013 Aug;146(2):119-33.
    doi: 10.1530/REP-13-0007pubmed: 23722152google scholar: lookup
  21. Weller MG. Ten Basic Rules of Antibody Validation.. Anal Chem Insights 2018;13:1177390118757462.
    doi: 10.1177/1177390118757462pmc: PMC5813849pubmed: 29467569google scholar: lookup
  22. Renner M, Bergmann G, Krebs I, End C, Lyer S, Hilberg F, Helmke B, Gassler N, Autschbach F, Bikker F, Strobel-Freidekind O, Gronert-Sum S, Benner A, Blaich S, Wittig R, Hudler M, Ligtenberg AJ, Madsen J, Holmskov U, Annese V, Latiano A, Schirmacher P, Amerongen AV, D'Amato M, Kioschis P, Hafner M, Poustka A, Mollenhauer J. DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn's disease.. Gastroenterology 2007 Nov;133(5):1499-509.
    doi: 10.1053/j.gastro.2007.08.007pubmed: 17983803google scholar: lookup
  23. Janssen WJ, Stefanski AL, Bochner BS, Evans CM. Control of lung defence by mucins and macrophages: ancient defence mechanisms with modern functions.. Eur Respir J 2016 Oct;48(4):1201-1214.
    doi: 10.1183/13993003.00120-2015pmc: PMC5120543pubmed: 27587549google scholar: lookup
  24. Jianzhong H. The genetic predisposition and the interplay of host genetics and gut microbiome in Crohn disease.. Clin Lab Med 2014 Dec;34(4):763-70.
    doi: 10.1016/j.cll.2014.08.003pmc: PMC4254428pubmed: 25439275google scholar: lookup
  25. Wu J, Miao Y, Abraham SN. The multiple antibacterial activities of the bladder epithelium.. Ann Transl Med 2017 Jan;5(2):35.
    doi: 10.21037/atm.2016.12.71pmc: PMC5300852pubmed: 28217700google scholar: lookup
  26. Ren S, Chen X, Jiang L, Zhu B, Jiang Q, Xi X. Deleted in malignant brain tumors 1 protein is a potential biomarker of acute respiratory distress syndrome induced by pneumonia.. Biochem Biophys Res Commun 2016 Sep 23;478(3):1344-9.
    doi: 10.1016/j.bbrc.2016.08.125pubmed: 27565730google scholar: lookup
  27. Müller H, End C, Weiss C, Renner M, Bhandiwad A, Helmke BM, Gassler N, Hafner M, Poustka A, Mollenhauer J, Poeschl J. Respiratory Deleted in Malignant Brain Tumours 1 (DMBT1) levels increase during lung maturation and infection.. Clin Exp Immunol 2008 Jan;151(1):123-9.
    doi: 10.1111/j.1365-2249.2007.03528.xpmc: PMC2276934pubmed: 17991292google scholar: lookup
  28. Müller H, Nagel C, Weiss C, Mollenhauer J, Poeschl J. Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells.. BMC Pulm Med 2015 Apr 8;15:32.
    doi: 10.1186/s12890-015-0027-xpmc: PMC4426184pubmed: 25885541google scholar: lookup
  29. Bullone M, Vargas A, Elce Y, Martin JG, Lavoie JP. Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma.. Sci Rep 2017 Aug 18;7(1):8843.
    doi: 10.1038/s41598-017-09414-8pmc: PMC5562887pubmed: 28821845google scholar: lookup
  30. Bullone M, Hélie P, Joubert P, Lavoie JP. Development of a Semiquantitative Histological Score for the Diagnosis of Heaves Using Endobronchial Biopsy Specimens in Horses.. J Vet Intern Med 2016 Sep;30(5):1739-1746.
    doi: 10.1111/jvim.14556pmc: PMC5032871pubmed: 27527123google scholar: lookup
  31. Dunican EM, Watchorn DC, Fahy JV. Autopsy and Imaging Studies of Mucus in Asthma. Lessons Learned about Disease Mechanisms and the Role of Mucus in Airflow Obstruction.. Ann Am Thorac Soc 2018 Nov;15(Suppl 3):S184-S191.
    doi: 10.1513/AnnalsATS.201807-485AWpmc: PMC6322032pubmed: 30431352google scholar: lookup
  32. Zhang S, Huo X, Zhang Y, Huang Y, Zheng X, Xu X. Ambient fine particulate matter inhibits innate airway antimicrobial activity in preschool children in e-waste areas.. Environ Int 2019 Feb;123:535-542.
    doi: 10.1016/j.envint.2018.12.061pubmed: 30622078google scholar: lookup
  33. Zhang S, Huo X, Zhang Y, Lu X, Xu C, Xu X. The association of PM(2.5) with airway innate antimicrobial activities of salivary agglutinin and surfactant protein D.. Chemosphere 2019 Jul;226:915-923.
    doi: 10.1016/j.chemosphere.2019.04.032pubmed: 31509921google scholar: lookup
  34. Beeler-Marfisi J, Clark ME, Wen X, Sears W, Huber L, Ackerley C, Viel L, Bienzle D. Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses.. Am J Vet Res 2010 Jun;71(6):682-9.
    doi: 10.2460/ajvr.71.6.682pubmed: 20513185google scholar: lookup
  35. Polley S, Prescott N, Nimmo E, Veal C, Vind I, Munkholm P, Fode P, Mansfield J, Skyt Andersen P, Satsangi J, G Mathew C, Hollox EJ. Copy number variation of scavenger-receptor cysteine-rich domains within DMBT1 and Crohn's disease.. Eur J Hum Genet 2016 Aug;24(9):1294-300.
    doi: 10.1038/ejhg.2015.280pmc: PMC4851238pubmed: 26813944google scholar: lookup
  36. Blanc G, Font B, Eichenberger D, Moreau C, Ricard-Blum S, Hulmes DJ, Moali C. Insights into how CUB domains can exert specific functions while sharing a common fold: conserved and specific features of the CUB1 domain contribute to the molecular basis of procollagen C-proteinase enhancer-1 activity.. J Biol Chem 2007 Jun 8;282(23):16924-33.
    doi: 10.1074/jbc.M701610200pubmed: 17446170google scholar: lookup
  37. Kotlyar M, Pastrello C, Pivetta F, Lo Sardo A, Cumbaa C, Li H, Naranian T, Niu Y, Ding Z, Vafaee F, Broackes-Carter F, Petschnigg J, Mills GB, Jurisicova A, Stagljar I, Maestro R, Jurisica I. In silico prediction of physical protein interactions and characterization of interactome orphans.. Nat Methods 2015 Jan;12(1):79-84.
    doi: 10.1038/nmeth.3178pubmed: 25402006google scholar: lookup
  38. Rosenstiel P, Sina C, End C, Renner M, Lyer S, Till A, Hellmig S, Nikolaus S, Fölsch UR, Helmke B, Autschbach F, Schirmacher P, Kioschis P, Hafner M, Poustka A, Mollenhauer J, Schreiber S. Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion.. J Immunol 2007 Jun 15;178(12):8203-11.
    doi: 10.4049/jimmunol.178.12.8203pubmed: 17548659google scholar: lookup
  39. Mollenhauer J, Herbertz S, Holmskov U, Tolnay M, Krebs I, Merlo A, Schrøder HD, Maier D, Breitling F, Wiemann S, Gröne HJ, Poustka A. DMBT1 encodes a protein involved in the immune defense and in epithelial differentiation and is highly unstable in cancer.. Cancer Res 2000 Mar 15;60(6):1704-10.
    pubmed: 10749143
  40. Bikker FJ, End C, Ligtenberg AJM, Blaich S, Lyer S, Renner M, Wittig R, Nazmi K, van Nieuw Amerongen A, Poustka A, Veerman ECI, Mollenhauer J. The scavenging capacity of DMBT1 is impaired by germline deletions.. Immunogenetics 2017 Jun;69(6):401-407.
    doi: 10.1007/s00251-017-0982-xpmc: PMC5435793pubmed: 28364129google scholar: lookup
  41. Panchenko AR, Madej T. Structural similarity of loops in protein families: toward the understanding of protein evolution.. BMC Evol Biol 2005 Feb 3;5:10.
    doi: 10.1186/1471-2148-5-10pmc: PMC549550pubmed: 15691378google scholar: lookup
  42. Choi Y, Deane CM. FREAD revisited: Accurate loop structure prediction using a database search algorithm.. Proteins 2010 May 1;78(6):1431-40.
    doi: 10.1002/prot.22658pubmed: 20034110google scholar: lookup
  43. Kodric M, Shah AN, Fabbri LM, Confalonieri M. An investigation of airway acidification in asthma using induced sputum: a study of feasibility and correlation.. Am J Respir Crit Care Med 2007 May 1;175(9):905-10.
    doi: 10.1164/rccm.200607-940OCpubmed: 17290044google scholar: lookup

Citations

This article has been cited 4 times.
  1. Ge Y, Liu X, Chen H, Li G, Xing X, Liu J, Zhang C, Zhuge Y, Wang F. The serum soluble scavenger with 5 domains levels: A novel biomarker for individuals with heart failure.. Front Physiol 2023;14:1140856.
    doi: 10.3389/fphys.2023.1140856pubmed: 37123263google scholar: lookup
  2. Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.. Animals (Basel) 2022 Mar 16;12(6).
    doi: 10.3390/ani12060744pubmed: 35327141google scholar: lookup
  3. Lee GKC, Kang H, Beeler-Marfisi J, Sears W, Lillie BN, Bienzle D. Effects of equine SALSA on neutrophil phagocytosis and macrophage cytokine production.. PLoS One 2022;17(3):e0264911.
    doi: 10.1371/journal.pone.0264911pubmed: 35286327google scholar: lookup
  4. Lee GKC, Beeler-Marfisi J, Viel L, Piché É, Kang H, Sears W, Bienzle D. Bronchial brush cytology, endobronchial biopsy, and SALSA immunohistochemistry in severe equine asthma.. Vet Pathol 2022 Jan;59(1):100-111.
    doi: 10.1177/03009858211048635pubmed: 34903109google scholar: lookup
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