Chemokine families CX3C chemokines

Chemokine receptors are a family of G protein-coupled receptors that contain seven transmembrane domains. Chemokine receptors are present on the cell surface membrane of leukocytes. As was the case for chemokines, these receptors are also divided into four subgroups CCR is specific for CC chemokines, CXCR for CXC chemokines, XCR1 for C chemokines and CX3CR1 for CX3C chemokines. The CC chemokine receptor family has eleven members, the CXC chemokine receptor family has seven members, and both the C chemokine receptor family and the CX3C chemokine receptor family have one member each. The signal transduction is mediated via the standard G protein-dependent pathway. 

Chemokine family. The mediators are divided into four subclasses according to chemical characteristics of the ligands, namely the number or positions of cyteine residues, as follows CC chemokines CXC chemokines CX3C chemokine C chemokines. These chemokines act at receptors largely named after the peptides themselves, and include CCCRl-8 and CXRl-4. (Chemokines recognized include MIP-la MIP-ip MCP-1 MCP-2 MCP-3 MCP-4 MIP-5 RANTES LCRl leukotactin-1 eotaxin, eotaxin-1 and some other chemokines. 

Chemokines are a superfamily of small proteins which play a crucial role in immune and inflammatory reactions and in viral infection (Hedrick and Zlotnik, 1996 Baggi-olini et al, 1997 Rollins, 1997). Most chemokines cause migration of leukocytes, but these molecules also affect angiogenesis, proliferation of hematopoietic precursors, and viral responses. Based on a cysteine motif, a CXC, CC, C and CX3C family have been identified (Fig. 1). CXC (or a) chemokines are active on neutrophils and lymphocytes while CC (or (3) chemokines exert their action on multiple leukocyte subtypes, including monocytes, basophils, eosinophils, T-lymphocytes, dendritic cells (DC) and NK cells, but they are generally inactive on PMN. Eotaxins... 

Chemokines are a family of pro-inflammatory activation-inducible cytokines or small protein signals secreted by cells. Chemokines induce directed chemotaxis in nearby responsive cells and therefore the name c/iemotactic cytokines. Four types of chemokines exist (1) C chemokine the first and the third conserved cysteine residues in the mature protein are missing (2) CC chemokine the first two conserved cysteine residues are adjacent in the mature protein (3) CXC chemokine one amino acid residue separates the first two conserved cysteine residues in the mature protein and (4) CX3C chemokine three amino acid residues separate the first two conserved cysteine residues in the mature protein. 

Structural criteria originally led to the classification of the nearly 50 known chemokines in four families, C, CC, CXC, and CX3C. Today scientists refer to them as constitutive chemokines, which are usually regulated during development, and as inducible chemokines, whose expression is regulated mainly during inflammatory processes. 

The chemokines are a family of small (8-12kDa) secreted chemoattractant cytokines that share a common structure dictated by the pattern of disulfide bonds that form between conserved cysteine (C) residues. The number and spacing of cysteines in the amino-terminus defines four chemokine classes, CXC, CC, XC and CX3C, where X represents any amino acid (aa) except C (Baggiolini and Loetscher 2000). A majority of chemokines have two sets of disulfide bonds formed by the pairing the first two cysteines (Ci and C2) with two others in a C1-C3 and C2-C4 pattern. These secreted proteins bind to G protein-coupled heptahelical receptors found on leukocytes that are designated by the class of chemokine bound (CXCRs, CCRs, XCRs, and CX3CR, respectively) (Rossi and Zlotnik 2000). 

Figure 1 Representative chemokines of CC (A), CXC(B), CX3C (C), and XC (D) families. The conserved cysteine pattern is shown in yeiiow (gray in the print version) sticks residues separating the two N-terminai cysteines are shown as magenta balls (B and C). Loops believed to be involved in coordinating the N-terminus of the receptor (N-loop and 40s-loop) are colored blue (dark gray in the print version) and charged residues in these regions are shown as sticks.

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