Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Heinemann, A; Hartnell, A; Stubbs, VE; Murakami, K; Soler, D; LaRosa, G; Askenase, PW; Williams, TJ; Sabroe, I.
Basophil responses to chemokines are regulated by both sequential and cooperative receptor signaling.
J Immunol. 2000; 165(12): 7224-7233.
Doi: 10.4049/jimmunol.165.12.7224
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- Führende Autor*innen der Med Uni Graz
- Heinemann Akos
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- Abstract:
- 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-3Ralpha (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-1alpha > 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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- Basophils - cytology
- Cell Size - immunology
- Chemokine CCL2 - metabolism
- Chemokines - blood
- Cytokines - blood
- Eosinophils - cytology
- Flow Cytometry - cytology
- Humans - cytology
- Ion Channel Gating - cytology
- Leukocytes, Mononuclear - cytology
- Monocyte Chemoattractant Proteins - pharmacology
- Monocytes - cytology
- Receptors, Chemokine - biosynthesis
- Scattering, Radiation - biosynthesis
- Signal Transduction - immunology