Skip to main content

Techniques Used in Pharmacological Evaluation of Histamine H4 Receptor Function on Native Human Eosinophils

  • Protocol
  • First Online:
Histamine Receptors as Drug Targets

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

  • 718 Accesses

Abstract

Most of the research on the histamine receptors in in vitro studies was accomplished using recombinant systems. These biological models proved to be ideal in the determination of the receptors’ function, biochemistry, and molecular signaling pathways. Unfortunately, they do not reflect the real biological situation, as the receptors are artificially introduced to host system and usually expressed in high quantity, not regulated as in native cells. Recently in order to overcome the limitations of recombinant systems, several important works were published that focus on the histamine receptors’ function in native human cells. For histamine H4 receptor functional studies immune cells, including human eosinophils, were mainly used. Therefore in this chapter we discuss the tools and provide step-by-step protocols used in the pharmacological evaluation of histamine H4 receptor function in primary human eosinophils. Methods include: isolation of human eosinophils from peripheral blood, functional determination of the effects of histamine receptors’ ligands (including selective histamine receptor agonists and antagonists), and data elaboration. We believe that the described methods may play an important role in future studies because as yet the function of histamine receptors on the other immune cells remains elusive.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Rothenberg ME, Hogan SP (2006) The eosinophil. Annu Rev Immunol 24:147–174

    Article  CAS  PubMed  Google Scholar 

  2. Rosenberg HF, Dyer KD, Foster PS (2013) Eosinophils: changing perspectives in health and disease. Nat Rev Immunol 13:9–22

    Article  CAS  PubMed  Google Scholar 

  3. Kita H (2011) Eosinophils: multifaceted biological properties and roles in health and disease. Immunol Rev 242:161–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Piliponsky AM, Gleich GJ, Bar I et al (2002) Effects of eosinophils on mast cells: a new pathway for the perpetuation of allergic inflammation. Mol Immunol 38:1369–1372

    Article  CAS  PubMed  Google Scholar 

  5. Ben-Zimra M, Bachelet I, Seaf M et al (2013) Eosinophil major basic protein activates human cord blood mast cells primed with fibroblast membranes by integrin-β1. Allergy 68:1259–1268

    Article  CAS  PubMed  Google Scholar 

  6. Weller PF (1994) Eosinophils: structure and functions. Curr Opin Immunol 6:85–90

    Article  CAS  PubMed  Google Scholar 

  7. Seifert R (2013) Functional selectivity of G-protein-coupled receptors: From recombinant systems to native human cells. Biochem Pharmacol 86:853–861

    Article  CAS  PubMed  Google Scholar 

  8. Ezeamuzie CI, Philips E (2000) Histamine H(2) receptors mediate the inhibitory effect of histamine on human eosinophil degranulation. Br J Pharmacol 131:482–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Buckland KF, Williams TJ, Conroy DM (2003) Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor. Br J Pharmacol 140:1117–1127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Pincus SH, DiNapoli AM, Schooley WR (1982) Superoxide production by eosinophils: activation by histamine. J Invest Dermatol 79:53–57

    Article  CAS  PubMed  Google Scholar 

  11. Reher TM, Brunskole I, Neumann D et al (2012) Evidence for ligand-specific conformations of the histamine H 2-receptor in human eosinophils and neutrophils. Biochem Pharmacol 84:1174–1185

    Article  CAS  PubMed  Google Scholar 

  12. Ling P, Ngo K, Nguyen S et al (2004) Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol 142:161–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Reher TM, Neumann D, Buschauer A et al (2012) Incomplete activation of human eosinophils via the histamine H4-receptor: evidence for ligand-specific receptor conformations. Biochem Pharmacol 84:192–203

    Article  CAS  PubMed  Google Scholar 

  14. Grosicki M, Kieć-Kononowicz K (2015) Human eosinophils-potential pharmacological model applied in human histamine H4 receptor research. Curr Med Chem 22:1–13

    Article  Google Scholar 

  15. Neubig RR, Spedding M, Kenakin T et al (2003) International union of pharmacology committee on receptor nomenclature and drug classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev 55:597–606

    Article  CAS  PubMed  Google Scholar 

  16. Seifert R, Schneider EH, Dove S et al (2011) Paradoxical stimulatory effects of the “standard” histamine H4-receptor antagonist JNJ7777120: the H4 receptor joins the club of 7 transmembrane domain receptors exhibiting functional selectivity. Mol Pharmacol 79:631–638

    Article  CAS  PubMed  Google Scholar 

  17. Nijmeijer S, Vischer HF, Sirci F et al (2013) Detailed analysis of biased histamine H4 receptor signalling by JNJ 7777120 analogues. Br J Pharmacol 170:78–88

    Google Scholar 

  18. Rosethorne EM, Charlton SJ (2011) Agonist-biased signaling at the histamine H4 receptor: JNJ7777120 recruits β-arrestin without activating G proteins. Mol Pharmacol 79:749–757

    Article  CAS  PubMed  Google Scholar 

  19. Dikalov S, Griendling KK, Harrison DG (2007) Measurement of reactive oxygen species in cardiovascular studies. Hypertension 49:717–727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Adamko DJ, Wu Y, Gleich GJ et al (2004) The induction of eosinophil peroxidase release: improved methods of measurement and stimulation. J Immunol Methods 291:101–108

    Article  CAS  PubMed  Google Scholar 

  21. Zhou M, Diwu Z, Panchuk-Voloshina N et al (1997) A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: applications in detecting the activity of phagocyte NADPH oxidase and other oxidases. Anal Biochem 253:162–168

    Article  CAS  PubMed  Google Scholar 

  22. Charlton SJ, Vauquelin G (2010) Elusive equilibrium: the challenge of interpreting receptor pharmacology using calcium assays. Br J Pharmacol 161:1250–1265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cooper JA (1987) Effects of cytochalasin and phalloidin on actin. J Cell Biol 105:1473–1478

    Article  CAS  PubMed  Google Scholar 

  24. Kernen P, Wymann MP, von Tscharner V et al (1991) Shape changes, exocytosis, and cytosolic free calcium changes in stimulated human eosinophils. J Clin Invest 87:2012–2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Blow N (2007) Cell migration: our protruding knowledge. Nat Methods 4:589–594

    Article  CAS  Google Scholar 

  26. Clark RA, Gallin JI, Kaplan AP (1975) The selective eosinophil chemotactic activity of histamine. J Exp Med 142:1462–1476

    Article  CAS  PubMed  Google Scholar 

  27. Ley K, Laudanna C, Cybulsky MI et al (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689

    Article  CAS  PubMed  Google Scholar 

  28. Thurau AM, Schylz U, Wolf V et al (1996) Identification of eosinophils by flow cytometry. Cytometry 23:150–158

    Article  CAS  PubMed  Google Scholar 

  29. Parsons ME, Ganellin CR (2009) Histamine and its receptors. Br J Pharmacol 147:127–135

    Article  Google Scholar 

  30. Seifert R, Wenzel-Seifert K, Burckstummer T et al (2003) Multiple differences in agonist and antagonist pharmacology between human and guinea pig histamine H1-receptor. J Pharmacol Exp Ther 305:1104–1115

    Article  CAS  PubMed  Google Scholar 

  31. Kraus A, Ghorai P, Birnkammer T et al (2009) N(G)-acylated aminothiazolylpropylguanidines as potent and selective histamine H(2) receptor agonists. ChemMedChem 4:232–240

    Article  CAS  PubMed  Google Scholar 

  32. Kitbunnadaj R, Hashimoto T, Poli E et al (2005) N-substituted piperidinyl alkyl imidazoles: discovery of methimepip as a potent and selective histamine H3 receptor agonist. J Med Chem 48:2100–2107

    Article  CAS  PubMed  Google Scholar 

  33. Lim HD, Smits RA, Bakker RA et al (2006) Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist. J Med Chem 49:6650–6651

    Article  CAS  PubMed  Google Scholar 

  34. Pertz HH, Elz S, Schunack W (2004) Structure-activity relationships of histamine H1-receptor agonists. Mini Rev Med Chem. 4:935–940

    Article  CAS  PubMed  Google Scholar 

  35. Lim HD, van Rijn RM, Ling P et al (2005) Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther 314:1310–1321

    Article  CAS  PubMed  Google Scholar 

  36. Kitbunnadaj R, Zuiderveld OP, Christophe B et al (2004) Identification of 4-(1H-imidazol-4(5)-ylmethyl)pyridine (immethridine) as a novel, potent, and highly selective histamine H(3) receptor agonist. J Med Chem 47:2414–2417

    Article  CAS  PubMed  Google Scholar 

  37. Liu C, Ma X, Jiang X et al (2001) Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol 59:420–426

    CAS  PubMed  Google Scholar 

  38. Janssens F, Leenaerts J, Diels G et al (2005) Norpiperidine imidazoazepines as a new class of potent, selective, and nonsedative H1 antihistamines. J Med Chem 48:2154–2166

    Article  CAS  PubMed  Google Scholar 

  39. Mahdy AM, Webster NR (2011) Histamine and antihistamines. Anaesth Intensive Care Med 12:324–329

    Article  Google Scholar 

  40. Jablonowski JA, Grice CA, Chai W et al (2003) The first potent and selective non-imidazole human histamine H4 receptor antagonists. J Med Chem 46:3957–3960

    Article  CAS  PubMed  Google Scholar 

  41. Beukers MW, Klaassen CH, De Grip WJ et al (1997) Heterologous expression of rat epitope-tagged histamine H2 receptors in insect Sf9 cells. Br J Pharmacol 122:867–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ohsawa Y, Hirasawa N (2014) The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical study. Allergol Int 63:533–542

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Polish National Science Center grant: “Research on human eosinophils as a potential therapeutic target” DEC/2014/13/N/NZ7/00897 and “Histamine H3/H4 receptors as an attractive target for the search of biologically active compounds” DEC/2011/02/A/NZ4/00031.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katarzyna Kieć-Kononowicz .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Grosicki, M., Kieć-Kononowicz, K. (2017). Techniques Used in Pharmacological Evaluation of Histamine H4 Receptor Function on Native Human Eosinophils. In: Tiligada, E., Ennis, M. (eds) Histamine Receptors as Drug Targets. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6843-5_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6843-5_8

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6841-1

  • Online ISBN: 978-1-4939-6843-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics