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*
Leukocyte Biology Section, Biomedical Sciences Division, Imperial College School of Medicine, South Kensington, London, United Kingdom; and
Millennium Pharmaceutical Inc., Cambridge, MA 002139
To investigate human basophil responses to chemokines, we have
developed a sensitive assay that uses flow cytometry to measure
leukocyte shape change as a marker of cell responsiveness. PBMC were
isolated from the blood of volunteers. Basophils were identified as a
single population of cells that stained positive for IL-3R
(CDw123)
and negative for HLA-DR, and their increase in forward scatter (as a
result of cell shape change) in response to chemokines was measured.
Shape change responses of basophils to chemokines were highly
reproducible, with a rank order of potency: monocyte chemoattractant
protein (MCP) 4 (peak at <1 nM) 
eotaxin-2 =
eotaxin-3 eotaxin > MCP-1 = MCP-3 >
macrophage-inflammatory protein-1 > RANTES = MCP-2 =
IL-8. The CCR4-selective ligand macrophage-derived chemokine did not
elicit a response at concentrations up to 10 nM. Blocking mAbs to CCR2
and CCR3 demonstrated that responses to higher concentrations (>10 nM)
of MCP-1 were mediated by CCR3 rather than CCR2, whereas MCP-4
exhibited a biphasic response consistent with sequential activation of
CCR3 at lower concentrations and CCR2 at 10 nM MCP-4 and above. In
contrast, responses to MCP-3 were blocked only in the presence of both
mAbs, but not after pretreatment with either anti-CCR2 or
anti-CCR3 mAb alone. These patterns of receptor usage were
different from those seen for eosinophils and monocytes. We suggest
that cooperation between CCRs might be a mechanism for preferential
recruitment of basophils, as occurs in tissue hypersensitivity
responses in vivo.
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