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Mast cells and basophils play an important role in IgEassociated allergic disorders and immune responses to parasites. Fc⑀RI cross-linking is a key event in the activation of mast cells and basophils. The Fc⑀RI is composed of three subunits: an ␣ chain, a ␤ chain, and a pair of ␥ chains, joined by a disulfide bond. The association of allergen with IgE bound to Fc⑀RI induces the transphosphorylation of cytoplasmic domains in the ␤-and ␥-chains called immunoreceptor tyrosinebased activation motifs via Lyn activation, which trigger signaling cascades leading to activation of kinases, phosphatases, or GTPases (1, 2). Fc⑀RI-mediated signaling induces a variety of events such as degranulation, increased gene transcription, and cytoskeleton rearrangement in mast cells and basophils (3, 4).Apart from the classical Fc⑀RI-mediated mechanism, mast cells and basophils are also activated by other substances such as chemokines and histamine-releasing factors (5, 6). Chemokines are a superfamily of small, structurally related cytokine molecules characterized by their ability to affect trafficking of immune cells. Some chemokines, such as CCL3 (macrophage inflammatory protein-1␣), CCL5 (RANTES), or CCL11 (eotaxin-1) have been reported to activate mouse, rat, or human mast cells and basophils in vitro (7-9) and in vivo (10, 11). In allergic inflammatory tissues, abundant expression of chemokines such as CCL3, CCL5, and CCL11 is observed both in the acute and late phase reactions (12, 13). It is therefore likely that Fc⑀RI and chemokine receptor engagement either occurs simultaneously or in relatively rapid succession in mast cells and basophils in vivo.Recently, Laffargue et al. (14) have shown that CCL3 or CCL5 significantly enhanced Fc⑀RI-mediated degranulation via phosphatidylinositol 3-kinase ␥-mediated signaling pathway in bone marrow-derived mast cells. The simultaneous engagement of Fc⑀RI and CC chemokine receptor (CCR) 1 appears to be important for optimal degranulation of mast cells in vitro and physiologically relevant levels of mast cell activation in vivo. However, it has not yet been established whether and how the simultaneous engagement of Fc⑀RI and CCR affects events other than degranulation of mast cells.In this paper, we show that costimulation via Fc⑀RI and CCR1 engagement synergistically enhances degranulation but inhibits CCL3-mediated chemotaxis using rat basophilic leukemia (RBL)-2H3 cells. Family members of the Rho-like GTPases, Rac, Cdc42, and Rho control cell motility by mediating the reorganization of the actin cytoskeleton (15-17). The costimulation via Fc⑀RI and CCR1 resulted in the imbalance of

Chemokines have a clearly defined role in mobilizing the recruitment of leukocytes to both healthy and inflamed tissues. This review details work from our and other laboratories, indicating that beta-chemokines may play important roles (i) in driving the terminal differentiation of mast cell precursors in mucosal tissues and (ii) in providing priming or costimulatory signals required for mast cell activation, leading to an antigen-driven inflammatory response. These data stem from in vivo, ex vivo, and in vitro studies. Data are also presented that suggest that Fc epsilon RI:chemokine receptor cross talk may involve spatiotemporal dynamics that may control the strength and nature of the complex activating signals controlling mast cell effector function.