High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines.

Abstract

Eosinophil leukocytes express high numbers of the chemokine receptor CCR3 which binds eotaxin, monocyte chemotactic protein (MCP)-4, and some other CC chemokines. In this paper we show that CCR3 is also highly expressed on human blood basophils, as indicated by Northern blotting and flow cytometry, and mediates mainly chemotaxis. Eotaxin and MCP-4 elicited basophil migration in vitro with similar efficacy as regulated upon activation normal T cells expressed and secreted (RANTES) and MCP-3. They also induced the release of histamine and leukotrienes in IL-3-primed basophils, but their efficacy was lower than that of MCP-1 and MCP-3, which were the most potent stimuli of exocytosis. Pretreatment of the basophils with a CCR3-blocking antibody abrogated the migration induced by eotaxin, RANTES, and by low to optimal concentrations of MCP-4, but decreased only minimally the response to MCP-3. The CCR3-blocking antibody also affected exocytosis: it abrogated histamine and leukotriene release induced by eotaxin, and partially inhibited the response to RANTES and MCP-4. In contrast, the antibody did not affect the responses induced by MCP-1, MCP-3, and macrophage inflammatory protein-1 ␣ , which may depend on CCR1 and CCR2, two additional receptors detected by Northern blotting with basophil RNA. This study demonstrates that CCR3 is the major receptor for eotaxin, RANTES, and MCP-4 in human basophils, and suggests that basophils and eosinophils, which are the characteristic effector cells of allergic inflammation, depend largely on CCR3 for migration towards different chemokines into inflamed tissues. ( J. Clin. Invest. 1997. 100:1137-1143.)

Honey is potentially effective in the treatment of atopic dermatitis: Clinical and mechanistic studies

“…Chemokine receptor (CCR)3 is a common receptor to all three chemokines 29, its expression is up regulated in AD lesions 30, and its blockade by monoclonal antibodies inhibits eosinophils recruitment 31. CCR3 is also expressed on basophils 32, mast cells 33, and activated Th2 cells 34. Therefore, honey's significant down regulation of IL4‐induced CCL26 release by keratinocytes could explain, at least partly, our clinical findings.…”

EMR1, the human homolog of F4/80, is an eosinophil‐specific receptor

“…In BM, we observed that also CCR3 dim cells, which according to studies in mice may represent immature eosinophils [19], were EMR1 + . Notably, while CCR3 and Siglec-8 are also expressed by basophils [20,21], EMR1 was absent on basophils and thus is a highly specific marker for eosinophils in humans (Fig. 2E, Table 1).…”

Eotaxin/CCL11 Suppresses IL-8/CXCL8 Secretion from Human Dermal Microvascular Endothelial Cells

“…Eotaxin/CCL11 is a member of the CC chemokine family that has potent chemotactic activity for eosinophils (15,16), basophils (17), mast cells (18), and Th2-type lymphocytes (19). Eotaxin/ CCL11 protein is up-regulated in a variety of inflammatory diseases possessing an eosinophilic component, such as allergic asthma (20,21), chronic sinusitis (22), and allergic rhinitis (23), and is thought to be a key player in the pathogenesis of these conditions.…”