FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Respiratory research2025; 26(1); 126; doi: 10.1186/s12931-025-03194-w

MARCKS protein is a potential target in a naturally occurring equine model of neutrophilic asthma.

Abstract: Asthma is a chronic inflammatory airway disease that affects millions of people worldwide. Horses develop asthma spontaneously and serve as a relevant model for multiple phenotypes and endotypes of human asthma. In horses with equine asthma (EA), environmental organic dust triggers increased inflammatory cytokines, excess airway mucus, reversible bronchoconstriction, and airway inflammation. In horses with severe EA (sEA), lower airway inflammation is invariably neutrophilic, making sEA a potential model for severe neutrophilic asthma in humans. Alveolar macrophages (AM) and airway neutrophils contribute to lower airway inflammation and tissue damage through the release of cytokines and toxic mediators including reactive oxygen species. Previous work shows that the Myristoylated Alanine Rich C Kinase Substrate (MARCKS) protein is increased in activated macrophages and neutrophils and is an essential regulator of inflammatory functions in these cell types. We hypothesized that MARCKS protein would be increased in bronchoalveolar lavage (BAL) cells from horses with EA, and that in vitro inhibition of MARCKS with a specific inhibitor peptide known as MyristoylAted N-terminal Sequence (MANS), would diminish cytokine production and respiratory burst. Methods: BAL cells from two populations of healthy and asthmatic horses were evaluated for cytology and MARCKS protein analysis. Isolated alveolar macrophages and peripheral blood neutrophils were stimulated with zymosan to evaluate MARCKS inhibition in cytokine secretion and respiratory burst. Results: We found increased levels of normalized MARCKS protein in total BAL cells from horses with asthma compared to normal horses. MARCKS inhibition with the MANS peptide had no effect on zymosan-stimulated release of tumor necrosis factor alpha (TNFα) or interleukin-8 (IL-8) from alveolar macrophages but did attenuate zymosan-stimulated respiratory burst in both alveolar macrophages and peripheral blood neutrophils. Conclusions: These findings point to a possible role for MARCKS in the pathophysiology of neutrophilic equine asthma and support further investigation of MARCKS as a novel anti-inflammatory target for severe neutrophilic asthma.
© 2025. The Author(s).
Get Full Text
Publication Date: 2025-04-02 PubMed ID: 40176021PubMed Central: PMC11967018DOI: 10.1186/s12931-025-03194-wGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

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.

The research article investigates the role of a protein called MARCKS in equine asthma (EA), a form of asthma in horses, which might also shed light on human asthma. It was found that the MARCKS protein was higher in horses with EA and it could be a potential target for therapeutic treatment.

Background

  • Equine asthma (EA) is a disease in horses, which parallels multiple phenotypes of human asthma.
  • The study is rooted in the hypothesis that Myristoylated Alanine Rich C Kinase Substrate (MARKS) protein, which is critical in regulating inflammation in alveolar macrophages and neutrophils (two types of defense cells in mammals), might be playing an essential role in EA.
  • Environmental organic dust is reported to intensify the symptoms in horses with severe EA (sEA) like excess mucus in the airway, bronchoconstriction, and airway inflammation.

Methods

  • Bronchoalveolar lavage (BAL) cells from healthy horses and horses with asthma were collected and evaluated for cytology and MARCKS protein levels.
  • A specific inhibitor peptide known as Myristoylated N-terminal Sequence (MANS), designed to suppress MARCKS, was used on alveolar macrophages and peripheral blood neutrophils to observe its effect on cytokine secretion and respiratory burst.

Results

  • The researchers found out that horses with asthma had notably higher levels of MARCKS protein than healthy horses.
  • Meanwhile, the MANS peptide was deemed ineffective in influencing the release of TNFα or IL-8 from alveolar macrophages.
  • However, it was successful in mitigating the zymosan-stimulated respiratory burst in both alveolar macrophages and peripheral blood neutrophils.

Conclusions

  • Based on the findings, the researchers suggested that MARCKS could be potentially influential in the pathophysiology of equine asthma, and can be a focus for further research on severe neutrophilic asthma.
  • As a novel anti-inflammatory target, MARCKS holds potential in the development of new treatment modalities for asthma.

Cite This Article

APA
Conley HE, Davis KU, Adler KB, Lavoie JP, Sheats MK. (2025). MARCKS protein is a potential target in a naturally occurring equine model of neutrophilic asthma. Respir Res, 26(1), 126. https://doi.org/10.1186/s12931-025-03194-w

Publication

Respiratory research
ISSN: 1465-993X
NlmUniqueID: 101090633
Country: England
Language: English
Volume: 26
Issue: 1
Pages: 126
PII: 126

Researcher Affiliations

Conley, Haleigh E
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
  • Comparative Medicine Institute, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
Davis, Kaori Uchiumi
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
  • Comparative Medicine Institute, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
Adler, Kenneth B
  • Comparative Medicine Institute, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
  • Department of Molecular and Biomedical Science, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
Lavoie, Jean-Pierre
  • Département des Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC, J2S 2M2, Canada.
Sheats, M Katie
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA. mkpeed@ncsu.edu.
  • Comparative Medicine Institute, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA. mkpeed@ncsu.edu.

MeSH Terms

  • Animals
  • Asthma / metabolism
  • Asthma / veterinary
  • Asthma / drug therapy
  • Asthma / immunology
  • Asthma / pathology
  • Horses
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Disease Models, Animal
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Horse Diseases / metabolism
  • Horse Diseases / drug therapy
  • Horse Diseases / immunology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / drug effects
  • Cytokines / metabolism
  • Cells, Cultured

Grant Funding

  • T32 OD011130 / NIH HHS
  • D17EQ-029 / Morris Animal Foundation

Conflict of Interest Statement

Declarations. Ethics approval and consent to participate: Procedures and protocols for population A were approved by the North Carolina State University Institutional Animal Care and Use Committee (IACUC 16-0740O and 19–779). Samples for Population B were obtained from the Equine Respiratory Tissue Bank (ERTB) (Lavoie laboratory). Consent for publication: Not applicable. Competing interests: HC - The author declares that they have no competing interests. KD - The author declares that they have no competing interests. KA - Patents planned, issued or pending: Biomarck Corporation, Durham, NC. METHODS FOR REGULATING INFLAMMATORY MEDIATORS AND PEPTIDES USEFUL THEREIN. Inventors: Kenneth Adler, Suji Takashi, Indu Parikh, Linda Martin, and Yuehuva Li.Assignment: BioMarck and NC State University. Filed: 6/4/2009 US Patent: 8,563,689; Granted: October 22, 2013. KD - The author declares that they have no competing interests. MKS - The author declares that they have no competing interests.

References

This article includes 83 references
  1. Hamilton D, Lehman H. Asthma phenotypes as a guide for current and biologic therapies.. Clin Rev Allergy Immunol 2020;59:160–74.
    pubmed: 31359247
  2. Wenzel S, Holgate ST. The mouse trap: it still yields few answers in asthma.. Am J Respir Crit Care Med 2006;174:1173–6.
    pubmed: 17110654doi: 10.1164/rccm.2609001google scholar: lookup
  3. Kips JC, Anderson GP, Fredberg JJ, Herz U, Inman MD, Jordana M, Kemeny DM, Lötvall J, Pauwels RA, Plopper CG. Murine models of asthma.. Eur Respir J 2003;22:374–82.
    pubmed: 12952276doi: 10.1183/09031936.03.00026403google scholar: lookup
  4. Martin RA, Hodgkins SR, Dixon AE, Poynter ME. Aligning mouse models of asthma to human endotypes of disease.. Respirology 2014;19:823–33.
    pmc: PMC4107015pubmed: 24811131doi: 10.1111/resp.12315google scholar: lookup
  5. Maltby S, Tay HL, Yang M, Foster PS. Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation.. Respirology 2017;22:874–85.
    pubmed: 28401621doi: 10.1111/resp.13052google scholar: lookup
  6. Woodrow JS, Sheats MK, Cooper B, Bayless R. Asthma. The Use of Animal Models and Their Translational Utility.. Cells 2023;12:1–25.
    pmc: PMC10093022pubmed: 37048164doi: 10.3390/cells12071091google scholar: lookup
  7. Bullone M, Lavoie J. The equine asthma model of airway remodeling: from a veterinary to a human perspective.. Cell Tissue Res 2020;380:223–36.
    pubmed: 31713728
  8. Mainguy-Seers S, Boivin R, Pourali Dogaheh S, Beaudry F, Hélie P, Bonilla AG, Martin JG, Lavoie JP. Effects of Azithromycin on bronchial remodeling in the natural model of severe neutrophilic asthma in horses.. Sci Rep 2022;12:1–11.
    pmc: PMC8748876pubmed: 35013387doi: 10.1038/s41598-021-03955-9google scholar: lookup
  9. Couëtil L, Cardwell J, Gerber V, Lavoie J, Léguillette R, EA R. Inflammatory airway disease of Horses–Revised consensus statement.. J Vet Intern Med 2016;30:503–15.
    pmc: PMC4913592pubmed: 26806374
  10. Ferrari CR, Cooley J, Mujahid N, Costa LR, Wills RW, Johnson ME, Swiderski CE. Horses with pasture asthma have airway remodeling that is characteristic of human asthma.. Vet Pathol 2018;55:144–58.
    pubmed: 29254472doi: 10.1177/0300985817741729google scholar: lookup
  11. Bond S, Léguillette R, Richard EA, Couetil L, Lavoie JP, Martin JG, Pirie RS. Equine asthma: integrative biologic relevance of a recently proposed nomenclature.. J Vet Intern Med 2018;32:2088–98.
    pmc: PMC6271326pubmed: 30294851doi: 10.1111/jvim.15302google scholar: lookup
  12. Sheats MK, Davis KU, Poole JA. Comparative review of asthma in farmers and horses.. Curr Allergy Asthma Rep 2019;19.
    pmc: PMC9116535pubmed: 31599358doi: 10.1007/s11882-019-0882-2google scholar: lookup
  13. Poole J, Romberger D. Immunological and inflammatory responses to organic dust in agriculture.. Curr Opin Allergy Clin Immunol 2012;12:126–32.
    pmc: PMC3292674pubmed: 22306554
  14. Qu J, Li Y, Zhong W, Gao P, Hu C. Recent developments in the role of reactive oxygen species in allergic asthma.. J Thorac Dis 2017;9:E32–43.
    pmc: PMC5303105pubmed: 28203435doi: 10.21037/jtd.2017.01.05google scholar: lookup
  15. Ammar M, Bahloul N, Amri O, Omri R, Ghozzi H, Kammoun S, Zeghal K, Ben Mahmoud L. Oxidative stress in patients with asthma and its relation to uncontrolled asthma.. J Clin Lab Anal 2022;36:e24345.
    pmc: PMC9102642pubmed: 35318723doi: 10.1002/jcla.24345google scholar: lookup
  16. Sahiner UM, Birben E, Erzurum S, Sackesen C, Kalayci O. Oxidative stress in asthma.. World Allergy Organ J 2011;4:151–8.
    pmc: PMC3488912pubmed: 23268432doi: 10.1097/wox.0b013e318232389egoogle scholar: lookup
  17. Cho YS, Moon H-B. The role of oxidative stress in the pathogenesis of asthma.. Allergy Asthma Immunol Res 2010;2:183–7.
    pmc: PMC2892050pubmed: 20592917doi: 10.4168/aair.2010.2.3.183google scholar: lookup
  18. Arbuzova A, Schmitz AAP, Res GV. Cross-talk unfolded: MARCKS proteins.. Biochem J 2002;362:1–12.
    pmc: PMC1222354pubmed: 11829734doi: 10.1042/0264-6021:3620001google scholar: lookup
  19. Sundaram M, Cook HW, Byers DM. The MARCKS family of phospholipid binding proteins: regulation of phospholipase D and other cellular components.. Biochem Cell Biol 2004;82:191–200.
    pubmed: 15052337
  20. Ziemba BP, Falke JJ. A PKC-MARCKS-PI. 3K regulatory module links Ca 2 + and PIP 3 signals at the leading edge of polarized macrophages.. PLoS ONE 2018;13:e0196678.
    pmc: PMC5929533pubmed: 29715315doi: 10.1371/journal.pone.0196678google scholar: lookup
  21. Green TD, Crews AL, Park J, Fang S, Adler KB. Regulation of mucin secretion and inflammation in asthma; A role for MARCKS protein?. Biochim Biophys Acta 2011;1810:1110–3.
    pmc: PMC3097255pubmed: 21281703doi: 10.1016/j.bbagen.2011.01.009google scholar: lookup
  22. Eckert RE, Neuder LE, Park J, Adler KB, Jones SL. Myristoylated Alanine-Rich C-Kinase substrate (MARCKS) protein regulation of human neutrophil migration.. Am J Respir Cell Mol Biol 2010;42:586–94.
    pmc: PMC2874444pubmed: 19574534doi: 10.1165/rcmb.2008-0394ocgoogle scholar: lookup
  23. Takashi S, Park J, Fang S, Koyama S, Parikh I, Adler KB. A peptide against the N-Terminus of myristoylated Alanine-Rich C kinase substrate inhibits degranulation of human leukocytes in vitro.. Am J Respir Cell Mol Biol 2006;34:647–52.
    pmc: PMC2644225pubmed: 16543603doi: 10.1165/rcmb.2006-0030rcgoogle scholar: lookup
  24. Sheats MK, Pescosolido KC, Hefner EM, Sung J, Adler KB, Jones SL. Myristoylated Alanine rich C kinase substrate (MARCKS) is essential to β2-integrin dependent responses of equine neutrophils.. Vet Immunol Immunopathol 2014;160:167–76.
    pmc: PMC4108539pubmed: 24857637doi: 10.1016/j.vetimm.2014.04.009google scholar: lookup
  25. Li J, D’Annibale-Tolhurst M, Adler K, Al E. A myristoylated alanine-rich C kinase substrate-related peptide suppresses cytokine mRNA and protein expression in LPS-activated canine neutrophils.. Am J Respir Cell Mol Biol 2013;48:314–21.
    pmc: PMC3604091pubmed: 23221047
  26. Green TD, Park J, Yin Q, Fang S, Crews AL, Jones SL, Adler KB. Directed migration of mouse macrophages in vitro involves myristoylated alanine-rich C-kinase substrate (MARCKS) protein.. J Leukoc Biol 2012;92:633–9.
    pmc: PMC3427602pubmed: 22623357doi: 10.1189/jlb.1211604google scholar: lookup
  27. Thelen M, Rosen A, Nairn AC, Aderem A. Tumor necrosis factor alpha modifies agonist-dependent responses in human neutrophils by inducing the synthesis and myristoylation of a specific protein kinase C substrate.. Proc. Nati. Acad. Sci. USA 1990;87:5603–5607.
    pmc: PMC54375pubmed: 2116001
  28. Wang C-N, Lin Y-C, Chang B-C, Chen C-H, Wu R, Lee C-C. Targeting the phosphorylation site of myristoylated alanine-rich C kinase substrate alleviates symptoms in a murine model of steroid-resistant asthma.. Br J Pharmacol 2019;176:1122–34.
    pmc: PMC6451065pubmed: 30706455doi: 10.1111/bph.14596google scholar: lookup
  29. Tilley P, Sales Luis JP, Branco Ferreira M. Correlation and discriminant analysis between clinical, endoscopic, thoracic X-ray and Bronchoalveolar lavage fluid cytology scores, for staging horses with recurrent airway obstruction (RAO).. Res Vet Sci 2012;93:1006–14.
    pubmed: 22136797
  30. Davis KU, Sheats MK. Bronchoalveolar lavage cytology characteristics and seasonal changes in a herd of pastured teaching horses.. Front Vet Sci 2019;6:74.
    pmc: PMC6426765pubmed: 30923711doi: 10.3389/fvets.2019.00074google scholar: lookup
  31. Lavoie JP, Leguillette R, Pasloske K, Charette L, Sawyer N, Guay D, Murphy T, Hickey GJ. Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction.. Am J Vet Res 2002;63:579–85.
    pubmed: 11939323
  32. Davarinejad H. accessed on Dec 13, Quantifications of Western Blots with ImageJ Available online: https://www.yorku.ca/yisheng/Internal/Protocols/ImageJ.pdf (2024).
  33. Ainsworth D, Wagner B, Franchini M, Grunig G, Erb H, Tan J. Time-dependent alterations in gene expression of interleukin-8 in the bronchial epithelium of horses with IFN-gamma and IL-8 production in Bronchoalveolar lavage cells.. Am J Vet Res 2006;67:669–77.
    pubmed: 16579761
  34. Giguère S, Viel L, Lee E, MacKay R, Hernandez J, Franchini M. Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.. Vet Immunol Immunopathol 2002;85:147–58.
    pubmed: 11943316
  35. Horohov D, Beadle R, Mouch S, Pourciau S. Temporal regulation of cytokine mRNA expression in equine recurrent airway obstruction.. Vet Immunol Immunopathol 2005;108:237–45.
    pubmed: 16098607
  36. Lee SM, Suk K, Lee WH. Myristoylated alanine-rich C kinase substrate (MARCKS) regulates the expression of Proinflammatory cytokines in macrophages through activation of p38/JNK MAPK and NF-κB.. Cell Immunol 2015;296:115–21.
    pubmed: 25929183doi: 10.1016/j.cellimm.2015.04.004google scholar: lookup
  37. Ivester K, Couëtil L, Moore G. An observational study of environmental exposures, airway cytology, and performance in racing thoroughbreds.. J Vet Intern Med 2018;32:1754–62.
    pmc: PMC6189343pubmed: 30222207
  38. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury.. Antioxid Redox Signal 2014;20:1126–67.
    pmc: PMC3929010pubmed: 23991888doi: 10.1089/ars.2012.5149google scholar: lookup
  39. Bullone M, Lavoie J. The contribution of oxidative stress and Inflamm-Aging in human and equine asthma.. Int J Mol Sci 2017;18.
    pmc: PMC5751215pubmed: 29206130
  40. Paola Rosanna D, Salvatore C. Reactive oxygen species, inflammation, and lung diseases.. Curr Pharm Des 2012;18:3889–900.
    pubmed: 22632750doi: 10.2174/138161212802083716google scholar: lookup
  41. Sheats MK, Yin Q, Fang S, Park J, Crews AL, Parikh I, Dickson B, Adler KB. MARCKS and lung disease.. Americcan J Respir Cell Mol Biol 2019;60:16–27.
    pmc: PMC6348718pubmed: 30339463doi: 10.1165/rcmb.2018-0285trgoogle scholar: lookup
  42. Chen C-H, Thai P, Yoneda K, Adler KB, Yang P-C, Wu R. A peptide that inhibits function of myristoylated Alanine-Rich C kinase substrate (MARCKS) reduces lung cancer metastasis.. Oncogene 2014;33:3696–706.
    pmc: PMC4631387pubmed: 23955080doi: 10.1038/onc.2013.336google scholar: lookup
  43. Li Y, Martin LD, Spizz G, Adler KB. MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro.. J Biol Chem 2001;276:40982–90.
    pubmed: 11533058doi: 10.1074/jbc.m105614200google scholar: lookup
  44. Agrawal A, Rengarajan S, Adler KB, Ram A, Ghosh B, Fahim M, Dickey BF. Inhibition of mucin secretion with MARCKS-related peptide improves airway obstruction in a mouse model of asthma.. J Appl Physiol 2007;102:399–405.
    pubmed: 16946028
  45. Yin Q, Fang S, Park J, Crews AL, Parikh I, Adler KB. An inhaled inhibitor of myristoylated Alanine-Rich C kinase substrate reverses LPS-Induced acute lung injury in mice.. Am J Respir Cell Mol Biol 2016;55:617–22.
    pmc: PMC5105187pubmed: 27556883doi: 10.1165/rcmb.2016-0236rcgoogle scholar: lookup
  46. Adler K, Kraft M, Parikh I, Murphy E, Van As A. Results of a phase 2a clinical trial with a peptide inhibitor of MARCKS protein indicate improvement of indices of bronchitis and lung function in patients with COPD.. Eur Respir J 2011;38:4901.
  47. Anderson WH, Ceppe A, Rice C, Meyer NJ, Rice TW, Gibbs K, Adler KB, Carson SS. A Phase II. Placebo-Controlled, Multicenter Pilot Study to Evaluate the Safety and Efficacy of BIO­-11006 Inhalation Solution in Patients with Acute Respiratory Distress Syndrome.. In Proceedings of the TP52. TP052 ARDS STUDIES 2021;p. 2668.
  48. Padoan E, Ferraresso S, Pegolo S, Barnini C, Castagnaro M, Gargelloni L. Gene expression profiles of the Immuno-Transcriptome in equine asthma.. Animals 2022;13:4.
    pmc: PMC9817691pubmed: 36611613
  49. Bright LA, Dittmar W, Nanduri B, McCarthy FM, Mujahid N, Costa LR, Burgess SC, Swiderski CE. Modeling the pasture-associated severe equine asthma Bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation.. Vet Med Res Rep 2019;10:43–63.
    pmc: PMC6504673pubmed: 31119093
  50. Mainguy-Seers S, Beaudry F, Fernandez-Prada C, Martin JG, Lavoie JP. Neutrophil Extracellular Vesicles and Airway Smooth Muscle Proliferation in the Natural Model of Severe Asthma in Horses.. Cells 2022;11:3347.
    pmc: PMC9653818pubmed: 36359743
  51. Vargas A, Roux-Dalvai F, Droit A, Lavoie JP. Neutrophil-derived exosomes: A new mechanism contributing to airway smooth muscle remodeling.. Am J Respir Cell Mol Biol 2016;55:450–61.
    pubmed: 27105177doi: 10.1165/rcmb.2016-0033ocgoogle scholar: lookup
  52. Ramery E, Closset R, Fabrice B, Art T, Lekeux P. Relevance of using a human microarray to study gene expression in heaves-affected horses.. Vet J 2008;117:216–21.
    pubmed: 17574458
  53. Hulliger MF, Pacholewska A, Vargas A, Lavoie JP, Leeb T, Gerber V, Jagannathan V. An integrative miRNA-mRNA expression analysis reveals striking transcriptomic similarities between severe equine asthma and specific asthma endotypes in humans.. Genes (Basel) 2020;11:1143.
    pmc: PMC7600650pubmed: 32998415
  54. Davis KU, Sheats MK. Differential gene expression and ingenuity pathway analysis of Bronchoalveolar lavage cells from horses with mild/moderate neutrophilic or mastocytic inflammation on BAL cytology.. Vet Immunol Immunopathol 2021;234:110195.
    pmc: PMC8132494pubmed: 33588285doi: 10.1053/j.gastro.2016.08.014.cagygoogle scholar: lookup
  55. Bubb MR, Lenox RH, Edison AS. Phosphorylation-dependent conformational changes induce a switch in the Actin-binding function of MARCKS.. J Biol Chem 1999;274:36472–8.
    pubmed: 10593944
  56. Huber R, Diekmann M, Hoffmeister L, Kühl F, Welz B, Brand K. MARCKS is an essential regulator of reactive oxygen species production in the monocytic cell type.. Antioxidants 2022;11:1600.
    pmc: PMC9404745pubmed: 36009319doi: 10.3390/antiox11081600google scholar: lookup
  57. Sheats MK, Sung EJ, Adler KB, Jones SL. In vitro neutrophil migration requires protein kinase c-delta (δ-PKC) mediated MARCKS (Myristoylated Alanine rich C-Kinase Substrate) phosphorylation.. Inflammation 2015;38:1126–41.
    pmc: PMC4888375pubmed: 25515270doi: 10.1007/s10753-014-0078-9google scholar: lookup
  58. Conley HE, Brown CF, Westerman TL, Elfenbein JR, Sheats MK. MARCKS Inhibition alters bovine neutrophil responses to Salmonella typhimurium.. Biomedicines 2024;12.
    pmc: PMC10886653pubmed: 38398044doi: 10.3390/biomedicines12020442google scholar: lookup
  59. Conley H, Till RL, Berglund AK, Jones SL, Sheats MK. A myristoylated alanine-rich C-kinase substrate (MARCKS) inhibitor peptide attenuates neutrophil outside-in β2-integrin activation and signaling.. Cell Adhes Migr 2023;17:1–16.
    pmc: PMC10348033pubmed: 37439125doi: 10.1080/19336918.2023.2233204google scholar: lookup
  60. Damera G, Jester WF, Jiang M, Zhao H, Fogle HW, Mittelman M, Haczku A, Murphy E, Parikh I, Panettieri RA. Inhibition of myristoylated alanine-rich C kinase substrate (MARCKS) protein inhibits ozone-induced airway neutrophilia and inflammation.. Exp Lung Res 2010;36:75–84.
    pmc: PMC4064305pubmed: 20205598doi: 10.3109/01902140903131200google scholar: lookup
  61. Lee C-C, Chen C-H, Kenyon NJ, Wang C-N, Tsai H-C, Chiu C-L, Chen Y, Forteza RM, Wu R. Inhibition of MARCKS phosphorylation attenuates of dendritic cell migration in a murine model of acute asthma.. Eur J Pharmacol 2024;980.
    pubmed: 39111683doi: 10.1016/j.ejphar.2024.176867google scholar: lookup
  62. Myat MM, Anderson S, Allen L-AAH, Aderem A. MARCKS regulates membrane ruffling and cell spreading.. Curr Biol 1997;7:611–4.
    pubmed: 9259558doi: 10.1016/s0960-9822(06)00262-4google scholar: lookup
  63. Rombouts K, Mello T, Liotta F, Galli A, Caligiuri A, Annunziato F, Pinzani M. MARCKS actin-binding capacity mediates actin filament assembly during mitosis in human hepatic stellate cells.. Am J Physiol Cell Physiol 2012.
    pubmed: 22555845doi: 10.1152/ajpcell.00093.2012.-cross-linkinggoogle scholar: lookup
  64. Toledo A, Zolessi FR, Arruti C. A novel effect of MARCKS phosphorylation by activated PKC: the dephosphorylation of its Serine 25 in chick neuroblasts.. PLoS ONE 2013;8:e62863.
    pmc: PMC3636281pubmed: 23634231doi: 10.1371/journal.pone.0062863google scholar: lookup
  65. Machlus KR, K WS, Stumpo DJ, Soussou TS, Paul DS, Campbell RA, Kalwa H, Michel T, Bergmeier W, Weyrich AS. Synthesis and dephosphorylation of MARCKS in the late stages of megakaryocyte maturation drive proplatelet formation.. Blood 2016;127:1468–80.
    pmc: PMC4797023pubmed: 26744461doi: 10.1182/blood-2015-08-663146google scholar: lookup
  66. Kim SS, Kim JH, Lee S-H, Chung SS, Bang O-S, Park D, Chung CH. Involvement of protein phosphatase-1-mediated MARCKS translocation in myogenic differentiation of embryonic muscle cells.. J Cell Sci 2022;115:2465–73.
    pubmed: 12045217doi: 10.1242/jcs.115.12.2465google scholar: lookup
  67. Brudvig JJ, Weimer JM, Cancedda L, Barnes AP, Newbern J. X MARCKS the spot: myristoylated alanine-rich C kinase substrate in neuronal function and disease.. Front Cell Neurosci 2015;9.
    pmc: PMC4602126pubmed: 26528135doi: 10.3389/fncel.2015.00407google scholar: lookup
  68. Barton A, Gehlen H. Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?. Mediators Inflamm 2016;2016.
    pmc: PMC5174180pubmed: 28053371
  69. Naylor J, Clark E, Clayton H. Chronic obstructive pulmonary disease: usefulness of clinical signs, Bronchoalveolar lavage, and lung biopsy as diagnostic and prognostic aids.. Can Vet J 1992;33:591–8.
    pmc: PMC1481327pubmed: 17424075
  70. Poole J, Gleason A, Bauer C, Al E. CD11c(+)/CD11b(+) cells are critical for organic dust-elicited murine lung inflammation.. Am J Respir Cell Mol Biol 2012;47:652–9.
    pmc: PMC3547108pubmed: 22822029
  71. Bullone M, Joubert P, Gagné A, Lavoie J, Hélie P. Bronchoalveolar lavage fluid neutrophilia is associated with the severity of pulmonary lesions during equine asthma exacerbations.. Equine Vet J 2018;50:609–15.
    pubmed: 29341228
  72. Brazil TJ, Dagleish MP, McGorum BC, Dixon PM, Haslett C, Chilvers ER. Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation.. Clin Exp Allergy 2005;35:854–65.
    pubmed: 16008670doi: 10.1111/j.1365-2222.2005.02231.xgoogle scholar: lookup
  73. Aharonson-Raz K, Lohmann KL, Townsend HG, Marques F, Singh B. Pulmonary intravascular macrophages as Proinflammatory cells in heaves, an asthma-like equine disease.. Am J Physiol Lung Cell Mol Physiol 2012;303:L189–98.
    pubmed: 22659880
  74. Underhill D. Macrophage recognition of zymosan particles.. J Endotoxin Res 2003;9:176–80.
    pubmed: 12831459
  75. Carballo E, Pitterle DM, Stumpo DJ, Sperling RT, Blackshear PJ. Phagocytic and Macropinocytic activity in MARCKS-deficient macrophages and fibroblasts.. Am J Physiol 1999;277:C163–73.
    pubmed: 10409119
  76. Baert K, Sonck E, Goddeeris B, Cox E. Complement receptor 3 plays a significant role in β-glucan induced ROS production by porcine neutrophils.. In Proceedings of the In New Perspectives on Immunity to Infection, Abstracts 2012.
  77. van Bruggen R, Drewniak A, Jansen M, van Houdt M, Roos D, Chapel H, Verhoeven AJ, Kuijper TW. Complement receptor 3, not Dectin-1, is the major receptor on human neutrophils for beta-glucan-bearing particles.. Mol Immunol 2009;47:575–81.
    pubmed: 19811837
  78. Serrander L, Larsson J, Lundqvist H, Lindmark M, Fällman M, Dahlgren C, Stendahl O. Particles binding β2-integrins mediate intracellular production of oxidative metabolites in human neutrophils independently of phagocytosis.. Biochim Biophys Acta - Mol Cell Res 1999;1452:133–44.
    pubmed: 10559466doi: 10.1016/s0167-4889(99)00123-8google scholar: lookup
  79. Qu J, Li Y, Zhong W, Gao P, Hu C. Recent developments in the role of reactive oxygen species in allergic asthma.. J Thorac Dis 2017;9(1):E32–43.
    pmc: PMC5303105pubmed: 28203435doi: 10.21037/jtd.2017.01.05google scholar: lookup
  80. Sahiner UM, Birben E, Erzurum S, Sackesen C, Kalayci O. Oxidative stress in asthma.. World Allergy Organ J 2011;4:151–8.
    pmc: PMC3488912pubmed: 23268432
  81. Nakamoto K, Watanabe M, Sada M, Inui T, Nakamura M, Honda K, Wada H, Mikami Y, Matsuzaki H, Horie M, Noguchi S. Serum reactive oxygen metabolite levels predict severe exacerbations of asthma.. PLoS ONE 2016;11(10):e0164948.
    pmc: PMC5077110pubmed: 27776186
  82. Message SD, Johnston SL. Host defense function of the airway epithelium in health and disease: clinical background.. J Leukoc Biol 2004;75:5–17.
    pmc: PMC7167170pubmed: 12972516doi: 10.1189/jlb.0703315google scholar: lookup
  83. Agrawal A, Murphy III, Park EC, Adler J, Parikh KB. BIO-11006, a novel MARCKS-related peptide, improves airway obstruction in a mouse model of mucus hypersecretion.. J Epithel Biol Pharmacol 2011;4:1–6.

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 106,180 horse owners like you who receive our email updates on horse health and nutrition.