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 FcɛRI 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.