chemokines

Introduction

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⁾

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

¹⁾