chemokines

see also:

• cytokines
• innate immunity

• chemokines are a chemotactic cytokines, that plays a crucial role in the immune system by directing the movement of immune cells, particularly leukocytes (white blood cells), to areas of inflammation or infection
• they bind to specific receptors on the surface of immune cells, triggering a cascade of events that leads to cell movement
• they are a superfamily of small, inducible, secreted, proinflammatory cytokines involved in a variety of immune responses, acting primarily as chemoattractants and activators of specific types of leukocytes
• they mediate their activities by binding to target cell surface chemokine receptors that belong to the large family of G protein-coupled, seven transmembrane domain receptors
• genes for many CXC and CC chemokines have been found to be clustered
• most of the CXC chemokines genes have been mapped to human chromosome 4q, and those for many CC chemokines on human chromosome 17q (mouse chromosome 11)¹⁾

• responsible for basal leukocyte migration
• include:
  • CCL14, CCL19, CCL20, CCL21, CCL25, CCL27, CXCL12 and CXCL13

• formed under pathological conditions or inflammatory stimuli such as IL-1, TNF-alpha, LPS, or viruses
• actively participate in the inflammatory response attracting immune cells to the site of inflammation
• include:
  • CXCL-8, CCL2, CCL3, CCL4, CCL5, CCL11, CXCL10

• defined by the arrangement of the conserved cysteine (C) residues of the mature proteins

• CXC chemokines have one amino acid (aa) residue separating the first two conserved cysteine residues
• four CXC chemokine receptors (CXCR-1 through 4)
• two sub groups:
  • ELR:
    • having the characteristic three aa sequence ELR (glutamic acid-leucine-arginine) motif immediately preceding the first conserved cysteine residue near the amino terminus
    • tend to be chemotactic for neutrophils
    • CXCL8 (aka IL-8)
      • implicated in mediator of gingivitis, psoriasis, colorectal cancer, malignant pleural mesothelioma, schizophrenia, other mental disorders, cystic fibrosis
      • associated with obesity
  • non-ELR:
    • lacking such an ELR domain
    • chemotactic for lymphocytes

• the CC chemokines in which the first two conserved cysteines residues are adjacent
• chemotactic for monocytes, T lymphocytes, B lymphocytes, dendritic cells, natural killer cells, eosinophils and basophils, but not neutrophils
• at least eight CC chemokine receptors (CCR-1 through 8)
• CCL2/CCR chemokine

• lack two (the first and third) of the four conserved cysteine residues
• the unique C chemokine lymphotactin was reported to be chemotactic for lymphocytes

• CX₃C chemokines have three intervening aa residues between the first two conserved cysteine residues
• one CX₃C chemokine receptor (CX₃CR)
• the sole CX₃C chemokine (fractalkine aka neurotactin), a type 1 membrane protein containing a chemokine domain tethered on a long mucin-like stalk, has been found to trigger the adhesion of T cells and monocytes