Chemokines

Chemokines are a family of small, secreted cytokines that regulate the movement of leukocytes by chemoattraction. They are typically 8 to 12 kilodaltons in size and exert their effects by binding to G protein–coupled receptors on target cells.

Chemokines are classified into four subfamilies by the arrangement of cysteines near the N-terminus: C, CC, CXC, and CX3C. Corresponding receptors are named CCR, CXCR, CX3CR, and XCR, reflecting the chemokine subfamilies they recognize. This classification mirrors both structural features and receptor usage that guide leukocyte trafficking.

Chemokine signaling directs leukocyte trafficking during development, homeostasis, infection, and inflammation. Binding to its receptor activates intracellular pathways that promote chemotaxis, adhesion, and cell activation, enabling leukocytes to exit blood vessels and migrate toward sites of injury or tissue remodeling. Production of chemokines is induced by pathogens and inflammatory stimuli in a variety of cells, including macrophages, dendritic cells, endothelial cells, and fibroblasts.

Examples and roles include CXCL8 (interleukin-8), a key neutrophil attractant; CCL2 (MCP-1) and CCL5 (RANTES), which recruit monocytes and T cells; and CX3CL1 (fractalkine), which exists in both membrane-bound and soluble forms. Chemokines also influence lymphoid tissue organization and angiogenesis in some contexts.

Clinical relevance encompasses contributions to inflammatory diseases, cancer, and infection. Therapeutic strategies aim to modulate chemokine signaling by targeting receptors, such as CCR5 antagonists used in HIV, though redundancy among chemokines and receptor promiscuity can limit efficacy.