Table 3. Functional analysis of chemokines and their receptors in vivo.
| Chemokine/receptor | Method | In vivo effect | Reference |
|---|---|---|---|
| Eotaxin (CCL11) | Neutralizing antibodies | Decrease in eosinophil recruitment, AHR | 33 |
| Neutralizing antibodies | Reduced Th2 recruitment, AHR | 61 | |
| Gene knockout | Partial reduction in eosinophil recruitment | 35 | |
| Gene knockout | No effect | 36 | |
| MCP-1 (CCL2) | Neutralizing antibodies | Reduction in AHR, lavage and tissue eosinophilia″and inflammatory mediator release | 33,48,78 |
| MCP-3 (CCL7) | Neutralizing antibodies | Reduced lavage eosinophilia | 79 |
| MCP-5 (CCL12) | Neutralizing antibodies | Reduction of tissue eosinophil recruitment and AHR | 33,80 |
| RANTES (CCL5) | Neutralizing antibodies | Reduced eosinophilia | 78 |
| Receptor antagonist | Reduction in tissue and lavage eosinophilia and AHR | 33 | |
| MIP-1α (CCL3) | Neutralizing antibodies | Reduced eosinophilia | 78 |
| Partial reduction in eosinophilia and AHR | 33 | ||
| MDC (CCL22) | Neutralizing antibodies | Reduction of tissue eosinophil recruitment and AHR | 55 |
| Reduced Th2 recruitment | 61 | ||
| TARC (CCL17) | Neutralizing antibodies | Reduction of tissue eosinophil recruitment, AHR and″decreased Th2 cytokine production | 59 |
| SDF-1α (CXCL12) | Neutralizing antibodies | Reduction of tissue eosinophil recruitment and AHR | 81 |
| CCR1 | Gene knockout | Decreased Th2 cytokines and airway remodelling | 82 |
| CCR2 | Gene knockout | Reduced airway hyper-reactivity and BAL histamine | 48 |
| Gene knockout | No effect | 83 | |
| Gene knockout | Increased inflammation, AHR and remodelling | 84 | |
| CCR4 | Gene knockout | No effect | 60 |
| CCR8 | Gene knockout | Decreased eosinophilia and serum IL-5 | 62 |
| CCR6 | Gene knockout | Decreased eosinophilia, AHR and lung IL-5 | 85 |
| IL-8R | Gene knockout | Increased B-cell recruitment, serum IgE and decreased AHR | 86 |
| CXCR4 | Neutralizing antibodies | Reduction of tissue eosinophil recruitment and AHR | 81 |
This table summarizes results from various investigators after abrogating chemokine ligand or receptor function by genetically deficient mice, neutralizing antibodies or receptor antagonists. The effect column denotes the resulting change in phenotype after intervention. For further details of each experiment please see individual references.
AHR, airway hyper-responsiveness; BAL, bronchoalveolar lavage; IgE, immunoglobulin E; IL-5, interleukin-5; IL-8R, interleukin-8 receptor; MCP, monocyte chemoattractant protein; MDC, macrophage-derived chemokine; MIP, macrophage inflammatory protein; RANTES, regulated upon activation, normal, T-cell expressed, and secreted; SDF-1, stromal-cell-derived factor 1; TARC, thymus and activation-regulated chemokine; Th2, T helper 2.