Table 1.
Tools to study CCL5.
| Tool (Developing company) | Definition and first description | Diseases studied |
|---|---|---|
| Deficient mice | ||
| CCL5-/- | Disruption of CCL5 expression, Makino et al.[12] | SLE, ischemic stroke, influenza inf., autoimmune nephritis, atherosclerosis, liver fibrosis, neuropathic pain, breast cancer |
| CCR1-/- | Disruption of CCR1 expression, Gao et al.[13] | Paramixovirus inf., RSV inf., leishmaniosis, MS, renal fibrosis, wound repair, cutaneous Arthus reaction, sepsis, hepatocellular carcinoma, neurological disease, RA, GVHD, myocardial infarction, Coronavirus inf. , renal ischemia-reperfusion injury, graft arterial disease |
| CCR3-/- | Disruption of CCR3 expression, Humbles et al.[14] | Allergic airway disease, asthma, lung remodeling and fibrosis, lung injury, allergic conjunctivitis, neuronal injury |
| CCR5-/- | Disruption of CCR5 expression, Zhou et al.[15] | HIV, EAE, colitis, transplant rejection and GVHD, cerebral malaria, hepatitis and hepatic fibrosis, C. Trachomatis inf., LCMV inf., RA, liver failure, Chagas disease, tuberculosis, arteriosclerosis, Y. pestis inf., autoimmune neuritis and gastritis, renal fibrosis, L. monocytogenes inf., CNS and neuronal injury, toxoplasmosis, alzheimer disease, ischemia-reperfusion injury, influenza inf., herpetic keratitis, COPD, genital herpes, pancreatitis, HSV inf., autoimmune uveoretinitis, cancer, japanese encephalitis, pain, nephritis, hypertension, allergic airway disease, encephalomyocarditis virus inf., S. mansoni inf., stroke. |
| Modified chemokines | ||
| Recombinant CCL5/RANTES (different suppliers) | Human, mouse and rat CCL5, expressed in bacteria | Viral infections, angiogenesis, cancer, allergic airway inflammation, arteriosclerosis, RA, EAE, and several other disease models. |
| Aminooxypentane (AOP)-RANTES (Merck Serono) (also PSC- and NNY-RANTES) | N-terminal chemically modified CCL5 with antagonistic activity, Simmons et al.[16] | HIV/SIV, RA, glomerulonephritis, tuberculosis, airway inflammation |
| Methionine (Met)-RANTES (Merck Serono) | CCL5 with retention of N-terminal methionine gained antagonistic activity, Proudfoot et al.[17] | HIV, RA, enteritis, transplant rejection, allergic pleurisy, airway inflammation, arteriosclerosis, colitis, RSV and pneumovirus inf., myocardial inflammation, Chagas disease, HSV inf., autoimmune gastritis and uveitis, EAE, wound healing, pancreatitis, angiogenesis, cancer, fever, bronchiolitis obliterans, neuropathic pain, periodontitis, |
| [44AANA47]-RANTES | CCL5 mutated at GAG binding site, impairs CCL5 oligomerization and function in vivo, Johnson et al.[18] | Peritonitis, airway inflammation, EAE, arteriosclerosis, RA, angiogenesis |
| [E66A]-RANTES | CCL5 mutated in oligomerization site, impairs CCL5 function in vivo, Baltus et al.[19] | Angiogenesis/arteriosclerosis |
| MKEY | Peptide inhibitor of CCL5/CXCL4 hetero dimerization, Iida et al.[20] | Aortic aneurism |
| Small-molecule inhibitors | ||
| TAK 220/779 (Takeda Chemical Industries) | CCR5 antagonists, Imamura et al.[21] and Baba et al.[22] | HIV |
| Maraviroc (Pfizer, Inc) | CCR5 antagonist, Fätkenheuer et al.[23] | HIV, RA , GVHD |
| SCH-C (Schering Plough) | CCR5 antagonist, Strizki et al.[24] | HIV |
| Vicriviroc (Schering Plough) | CCR5 antagonist, Strizki et al.[25] | HIV |
| YM-344031 (Astellas) | CCR3 antagonist, Suzuki et al.[26] | Skin allergy, Choroidal neovascularization |
| UCB 35625 (Banyu Pharmaceutical) | CCR1/CCR3 antagonist, Sabroe et al.[27] | HIV |
| CCX721/ CCX354 (Chemo Centryx) | CCR1 antagonists, Dairaghi et al.[28,29] | Myeloma bone disease, RA |
| BX471 (Berlex Biosciences) | CCR1 antagonist, Horuk et al.[30] | RA, MS, Lung injury, Kidney injury, heart transplant |
| MLN3897 (Millennium) | CCR1 antagonist, Vallet et al.[31] | RA, osteolytic bone disease |
| AZD4818 | CCR1 antagonist, Kerstjens et al.[32] | COPD |
| CP-481715 | CCR1 antagonist, Gladue et al.[33] | RA |
| Neutralizing antibodies | ||
| Anti-CCL5 (different companies) | Rat, mouse and human monoclonal and polyclonal antibodies | Viral infections, angiogenesis, cancer, allergic airway inflammation, atherosclerosis, RA, EAE, and several other disease models. |
| MAb d5d7 (VLST corporation) | Targets human CCL3, CCL4 and CCL5, Scalley-Kim et al.[34] | Skin inflammation |
| Nanobodies | Single domain camelid antibody fragment against CCL5, Blanchetot et al.[35] | Chemokine binding, chemokine receptor activation and chemotaxis |
| CCL5-binding proteins | ||
| Evasin 4 | CCL5/CCL11-binding protein, Déruaz et al.[36] | Colitis |
| M3 – Murine γ herpesvirus chemokine binding protein | Soluble, promiscuous binding protein, Parry et al.[37] | Murine γ herpesvirus-68 inf. |
| vCCI, 35K – viral CC chemokine inhibitor | Poxvirus-encoded soluble receptors, Smith et al.[38] | Allergic airway disease, RA, vaccinia virus inf., atherosclerosis, vein graft stenosis, peritonitis, hepatitis |
| M-T7 – mixoma virus T7 protein | IFN-γ/chemokine-binding protein, Lalani et al.[39] | Vascular injury, transplant rejection and angiogenesis |
| Miscelaneous | ||
| Immunization | Naked DNA vaccination inducing anti-CCL5 antibodies in rodents, Youssef et al.[40] | RA, EAE, T. cruzi infection |
Abbreviations: Inf: infection; SLE: Systemic lupus erythematosus; RA: Rheumatoid arthritis; RSV: Respiratory syncytial virus; MS: Multiple sclerosis; GVHD: Graft versus host disease; HIV: Human immunodeficiency virus; LCMV: lymphocytic choriomeningitis virus; COPD: Chronic obstructive pulmonary disease; HSV: Herpes simplex virus; EAE: Experimental autoimmune encephalomyelitis; SIV: Simian immunodeficiency vírus.
Description of the tools (animals, antibodies, modified chemokines, small molecules and chemokine-binding proteins) used for the study of CCL5 and its receptors in different experimental settings.