Histamine H4 antagonism: a therapy for chronic allergy? - PubMed (original) (raw)

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Histamine H4 antagonism: a therapy for chronic allergy?

Bruce L Daugherty. Br J Pharmacol. 2004 May.

No abstract available

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Figure 1

Mechanism of histamine-induced recruitment of eosinophils and mast cells in chronic allergic inflammation. Histamine H4 GPCRs are expressed on the surface of both eosinophils and mast cells. Antigen-IgE complex-dependent crosslinking of Fc_ɛ_RI on the surface of resident mast cells stimulates the secretion of histamine, which binds to and activates the H4 receptor on eosinophils. Signalling through the H4 receptor triggers a series of signal transduction events (calcium mobilization, actin polymerization, shape change, upregulation of adhesion molecule expression) leading to directional migration (chemotaxis) and accumulation of eosinophils into sites of inflammation. Upon release, histamine can also stimulate the recruitment of additional mast cells into the inflammatory site, by activation of the mast cell expressed H4 receptor. As shown in the figure, the H4 receptor is one of a number of G-protein coupled chemottractant receptors expressed on eosinophils. These include members of the chemokine receptor family, receptors for classical chemoattractants (complement cleavage fragments, formyl peptides and lipid mediators). Abbreviations: EOS, eosinophil; MC, mast cell; IgE, immunoglobulin E; H4, histamine receptor type 4; PAFR, platelet activating factor receptor; BLT1, leukotriene B4 receptor type 1; CysLT1, leukotriene D4 receptor type 1; CCR1, C-C chemokine receptor type 1; CCR3, C-C chemokine receptor type 3; CXCR2, C-X-C chemokine receptor type 2; CXCR4, C-X-C chemokine receptor type 4; C3aR, complement 3a receptor; C5aR, complement 5a receptor; f-MLFR, _N_-formyl-methionyl-leucyl-phenylalanine receptor.

Comment on

• Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor.
  Buckland KF, Williams TJ, Conroy DM. Buckland KF, et al. Br J Pharmacol. 2003 Nov;140(6):1117-27. doi: 10.1038/sj.bjp.0705530. Epub 2003 Oct 6. Br J Pharmacol. 2003. PMID: 14530216 Free PMC article.
• Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation.
  Ling P, Ngo K, Nguyen S, Thurmond RL, Edwards JP, Karlsson L, Fung-Leung WP. Ling P, et al. Br J Pharmacol. 2004 May;142(1):161-71. doi: 10.1038/sj.bjp.0705729. Br J Pharmacol. 2004. PMID: 15131002 Free PMC article.

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