RnDSy-lu-2945 Products for Chemokine Research The Chemokine Superfamily Chemokines are small cell surface-localized or secreted chemotactic cytokines that bind to and activate specific G protein-coupled chemokine receptors. Most chemokines have at least four conserved N-terminal cysteine residues that form two intramolecular disulfide bonds. Four chemokine subfamilies (CXC, CC, C and CX3C) have been defined based upon the placement of the first two cysteine residues. The CXC chemokine subfamily is characterized by two cysteine residues separated by one amino acid. Within this subfamily, two CXC classes are further defined by the presence or absence of an ELR motif sequence. ELR– CXC chemokines act as chemoattractants for lymphocytes, while ELR+ CXC chemokines are chemoattractants for neutrophils. Additionally, CXC chemokines can mediate angiogenesis.1 The CC chemokine subfamily is defined by two adjacent cysteine CCR1 H: CCL3-5, 7, 8, 13-16, 23, CCL3L1, CCL3L3, CCL4L1, CCL4L2 M: CCL3-7, 9/10 residues. CC chemokines induce inflammatory H: XCL1, 2 XCR1 responses via regulation of monocyte, M: XCL1 macrophage, mast cell, and T cell migration.2 H: CCL2, 7, 8, 13, 16 CCR2 (A or B) M: CCL2, 7, 12 C chemokines are characterized by a single H: CCL26 CX3CR1 cysteine residue and are constitutively expressed H: CX3CL1 in the thymus where they regulate T cell H: CCL5, 7, 8, 11, 13, 14, 15, 24, 26, 28, CCL3L1, CCL3L3 M: CX3CL1 CCR3 M: CCL5, 7, 9/10, 11, 24 differentiation.3 The CX3C chemokine subfamily is defined by two cysteine residues separated by H: CXCL6-8 CXCR1 three amino acids. Cell surface-localized CX3CL1/ H: CCL2, 3, 5, 17, 22 M: CXCL7, LIX CCR4 Fractalkine mediates leukocyte adhesion while M: CCL2, 3, 5, 17, 22 soluble CX3CL1/Fractalkine is chemotactic for H: CXCL1-3, 5-8 leukocytes.4 CX3CL1/Fractalkine is also a critical H: CCL3-5, 8, 11, 13, 14, 16, CCL3L1, M: CXCL1-3, 7, LIX CXCR2 CCR5 CCL3L3, CCL4L1, CCL4L2 regulator of microglia-neuron communication M: CCL3-5 during neural development.5 H: CXCL4, 9-11, 13, CXCL4L1 While chemokine receptors generally bind only CCR6 H: CCL20 M: CXCL4, 9-11 CXCR3 M: CCL20 one subfamily of chemokines, within those subfamilies, most chemokines display promiscuous receptor binding patterns. The CCR7 H: CCL19, 21 M: CCL19, 21 H: CXCL4, 9-11, CXCL4L1 CXCR3B redundancy of chemokine ligand-receptor binding may ensure robust signaling. In addition, promiscuous binding and non-signaling CCR8 H: CCL1, 4, 16, 17 M: CCL1, 8 H: CXCL12 CXCR4 chemokine receptors offer mechanisms by which M: CXCL12 chemokine signaling can be regulated by either subtle differences in receptor signaling or H: CCL25 CCR9 M: CCL25 differences in ligand-receptor expression H: CXCL13 M: CXCL13 CXCR5 patterns.6 Select chemokine ligands and receptors are implicated in HIV infection and H: CCL27, 28 CCR10 M: CCL27, 28 persistence, while aberrant chemokine H: CXCL16 expression and signaling is associated with M: CXCL16 CXCR6 pathological conditions including inflammatory CCR11 H: CCL2, 8, 13, 19, 21, 25 diseases and cancer.7-9 M: CCL19, 21, 25 References H: CXCL11, 12 CXCR7 1. Mehrad, B. et al. (2007) Thromb. Haemost. 97:755. M: CXCL11, 12 PITPNM3 H: CCL18 2. Ono, S.J. et al. (2003) J. Allergy Clin. Immunol. 111:1185. 3. Lei, Y. & Y. Takahama (2012) Microbes Infect. 14:262. H: CXCL14, 17 4. Jones, B.A. et al. (2010) Mol. Interv. 10:263. M: CXCL14, 17 Unknown 5. Wolf, Y. et al. (2013) Front. Cell. Neurosci. 7:26. CCRL2/CRAM-A/B H: CCL19 M: CXCL15 6. Bennett, L.D. et al. (2011) Immunology 134:246. 7. Evans, V.A. et al. (2012) Cytokine Growth Factor Rev. 23:151. 8. Balkwill, F.R. (2012) J. Pathol. 226:148. H: CCL1, 2, 5, 7, 8, 11, 13, 14, 16-18 9. White, G.E. et al. (2013) Pharmacol. Rev. 65:47. CCRL2/LCCR M: CCL19 M: CCL2, 11 H: CXCL1-3, 5, 6, 8 DARC M: CXCL1, 2, LIX H: CXCL4, 9-11, 13 D6 H: CCL2-5, 7, 8, 11, 13, 14, 17, 22, CCL3L1 M: CCL2, 3 Key H: Human M: Mouse C Chemokines/Receptors CXC ELR+ Chemokines/Receptors For additional information CC Chemokines/Receptors CX3C Chemokines/Receptors >RnDSystems.com/ChemokineInfoTable CXC ELR- Chemokines/Receptors Non-signaling Chemokine Receptors CXC Chemokines CXC Chemokines Recombinant & Recombinant CXC chemokines, also known as α chemokines, Molecule Natural Proteins Antibodies ELISAs Human Protein Sampler Packs are critical regulators of normal development CXCL1/2/3/GRO CR H (B/N, FC, WB) CR (B/N, WB) and immune responses. The CXC chemokine subfamily consists of nineteen ligands and H (B/N, E, FC, WB) M (B/N, E, WB) CXCL1/GROα/KC/CINC-1 H M R H M R R (B/N, IHC, WB) seven receptors. CXC chemokines that contain an ELR motif are potent angiogenic H (B/N, FC, WB) M (B/N, E, ICC, IHC, WB) CXCL2/GROβ/MIP-2/CINC-3 H M R CR M R factors, while ELR–CXC chemokines are R (B/N, E, WB) angiostatic. Select CXC chemokines and CXCL3/GROγ/CINC-2/DCIP-1 H M R H (B/N, FC, WB) M (B/N, WB) R (B/N, E, WB) R receptors regulate hematopoietic stem cell CXCL4/PF4 H M H (E, FC, WB) M (E, WB) H M migration. They are also involved in regulating CXCL5/ENA-70 H tumor progression and are of interest as targets 1-3 CXCL5/ENA-74 H for therapeutic intervention. References CXCL5/ENA-78 H H (B/N, E, FC, IHC, WB) H 1. Zhu, Q. et al. (2012) J. Mol. Histol. 43:699. CXCL6/GCP-2 H H (B/N, E, FC, WB) H 2. Vinader, V. & K. Afarinkia (2012) Future Med. Chem. 4:853. CXCL7/NAP-2 H H (B/N, E, WB) H 3. Owen, J.L. & M. Mohamadzadeh (2013) Front. Physiol. 4:159. CXCL7/Thymus Chemokine-1 M R M (B/N, E, IHC, WB) R (B/N, E, IHC, WB) M R 104 H (B/N, E, FC, ICC, IHC, WB) P (B/N, E, WB) CXCL8/IL-8 H P Ca F H P Ca F Ca (B/N, E, ICC, WB) F (B/N, E, ICC, WB) 103 CXCL9/MIG H M H (B/N, E, FC, ICC, WB) M (B/N, E, WB) H M H (B/N, E, FC, ICC, WB) M (B/N, E, IHC, WB) CXCL10/IP-10/CRG-2 H M CR H M CR (B/N, WB) 102 CXCL11/I-TAC H M H (B/N, E, WB) M (B/N, E, WB) H M CXCR5 CXCL12/SDF-1 H M F RM H (B/N, E, FC, IHC, WB) M (B/N, E, FC, IHC, WB) H M 1 CXCL12/SDF-1α H M F RM H M 10 CXCL12/SDF-1β H F H (B/N, E, WB) CXCL12/SDF-1γ H 100 CXCL13/BLC/BCA-1 H M H (B/N, E, FC, IHC, WB) M (B/N, E, IHC, WB) H M 100 101 102 103 104 B220/CD45R CXCL14/BRAK H M H (E, WB) M (WB) H Detection of CXCR5 and B220/CD45R on Mouse Splenocytes by Flow CXCL15/Lungkine M M (E, WB) M Cytometry. Mouse splenocytes were stained for CXCR5 and B220/CD45R expression using a PE-conjugated Rat Anti-Mouse CXCR5 Monoclonal Anti- CXCL16 H M H (B/N, E, FC, IHC, WB) M (B/N, E, FC, WB) H M body (Catalog # FAB6198P) and an APC-conjugated Rat Anti-Mouse B220/ CXCL17/VCC-1 H M H (FC, ICC, WB) M (WB) CD45R Monoclonal Antibody (Catalog # FAB1217A). Quadrants were set based on isotype controls. LIX M R M (B/N, E, WB) R (B/N, E, WB) M R CXCR1/IL-8 RA Antibody (µg/mL) 10-2 10-1 100 101 CXC Chemokine Receptors 6000 6000 Molecule Antibodies Tocris Biochemicals & Peptides 5000 5000 CXCR1/IL-8 RA H (B/N, FC, IHC) (Mean RFU) Migration Cell CXCR2/IL-8 RB H (B/N, FC, IHC) M (B/N, FC) 4000 4000 CXCR3 H (B/N, FC, IHC) M (FC) 3000 3000 CXCR4 H (B/N, FC, IHC) M (B/N, FC, ICC, IHC) F (FC, ICC) CXCR5 H (B/N, FC, ICC, IHC) M (FC, ICC) 2000 2000 Cell Migration (Mean RFU) Migration Cell CXCR6 H (FC) M (FC) 1000 1000 CXCR7/RDC-1 H (FC, IHC) M (FC, WB) DARC H (FC, ICC) M (FC, WB) R (FC, WB) 0 0 10-2 10-1 100 101 CXCL8/IL-8 (ng/mL) Species Key: H Human, M Mouse, R Rat, B Bovine, Ca Canine, CR Cotton Rat, F Feline, P Porcine, RM Rhesus Macaque, V Viral Chemotaxis Induced by CXCL8/IL‑8 and Neutralization using a Human Application Key: B/N Blocking/Neutralization, E ELISA (Cap. or Det.), FC Flow Cytometry, ICC Immunocytochemistry, IHC Immunohistochemistry, IP Immunoprecipitation, CXCR1/IL‑8 RA Antibody. Recombinant Human CXCL8/IL-8 (Catalog # WB Western Blot 208-IL) chemoattracts the BaF3 mouse pro-B cell line transfected with hu- man CXCR1/IL-8 RA in a dose-dependent manner (orange line). The amount of cells that migrated through to the lower chemotaxis chamber was mea- sured by Resazurin (Catalog # AR002). Chemotaxis elicited by 1 ng/mL Recombinant Human CXCL8/IL-8 was neutralized by increasing concentra- tions of Human CXCR1/IL-8 RA Monoclonal Antibody (Catalog # MAB330; green line). Learn more | rndsystems.com/chemokines CC Chemokines CC Chemokines Recombinant CC chemokines, also known as β chemokines, Molecule Recombinant & Antibodies ELISAs Human Protein are critical mediators of the inflammatory Natural Proteins Sampler Packs response.