NDLI: Histamine induces cytoskeletal changes in human eosinophils via the H4 receptor

Content Provider	PubMed Central
Author	Buckland, Karen F. Williams, Timothy J. Conroy, Dolores M.
Copyright Year	2003
Abstract	Histamine (0.004–2 μ M) induced a concentration-dependent shape change of human eosinophils, but not of neutrophils or basophils, detected as an increase in forward scatter (FSC) in the gated autofluorescence/forward scatter (GAFS) assay. The histamine-induced eosinophil shape change was completely abolished by thioperamide (10 μ M), an H3/H4 receptor antagonist, but was not inhibited by pyrilamine or cimetidine (10 μ M), H1 and H2 receptor antagonists, respectively. The H4 receptor agonists, clobenpropit and clozapine (0.004–2 μ M), which are also H3 receptor antagonists, both induced eosinophil shape change, which was inhibited by thioperamide (10 μ M). The H3/H4 receptor agonists, imetit, R-α-methyl histamine and N-α-methyl histamine (0.004–2 μ M) also induced eosinophil shape change. Histamine induced actin polymerisation (0.015–10 μ M), intracellular calcium mobilisation (10–100 μ M) and a significant upregulation of expression of the cell adhesion molecule CD11b (0.004–10 μ M) in eosinophils, all of which were inhibited by thioperamide (10–100 μ M). In addition, the H4 receptor agonist/H3 receptor antagonist clozapine (20 μ M) stimulated a rise in intracellular calcium in eosinophils. Activation of H4 receptors by histamine (1 μ M) primed eosinophils for increased chemotactic responses to eotaxin, but histamine (0.1–10 μ M) did not directly induce chemotaxis of eosinophils. Pertussis toxin (1 μg ml−1) inhibited shape change and actin polymerisation responses induced by histamine showing that these effects are mediated by coupling to a Gα i/o G-protein. This study demonstrates that human eosinophils express functional H4 receptors and may provide a novel target for allergic disease therapy.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0705530
Ending Page	1127
Page Count	11
Starting Page	1117
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	6
Volume Number	140
Language	English
Publisher Date	2003-11-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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