Ccl3

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, some virus types and bacteria. In humans, about 50 chemokines are currently known. A strongly conserved structural feature of all chemokines is a fixed group of cysteine residues that is stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for its fixed 3-dimensional structure.

In the CC chemokines, the cysteines follow each other directly (see figure), in the CXC chemokines they are separated (CC = acronym for cysteine-cysteine) by 1, in the CXXXC chemokines by 3 other amino acids. Chemokines are produced and secreted by a large number of immune cells. They transmit their signals by binding to chemokine receptors via G-proteins. Some chemokines have a pro-inflammatory effect, others have a regulatory effect on the development and homeostasis of tissues.

CCL3 also called "chemokines (C-C motif) ligand 3 or as "macrophage inflammatory protein 1-alpha" or MIP-1-alpha, is a human protein encoded by the gene located on chromosome 17: 36.09 - 36.09MB, CCL3.

Since about 3 decades 2 variants of CCL3 are known. They were originally called MIP-1-alpha and MIP-1-beta, but are now classified as CCL3 and CCL4. Both chemokines overlap in their effects.

CCL3 is a cytokine that belongs to the CC chemokine family. It is involved in acute inflammatory reactions of the organism by activating neutrophil granulocytes and attracting them to the site of inflammation. Monocytes and macrophages are also attracted. CCL3 acts by binding to the receptors CCR1 (see belowCCL1), CCR4 and CCR5.

CCL3 plays an initiating role in certain fever reactions. The fever induced by lipopolysaccharides (LPS) is prostaglandin-dependent on the one hand and prostaglandin-independent on the other. In addition to LPS-stimulated macrophages, the corticotropin-releasing factor (CRF), endothelin-1 (ET-1), interleukin-1 and CCL3 play a role in prostaglandin-independent fever reactions.

The expression of CCL3-induced fever reactions cannot be suppressed bycyclooxygenase inhibitors.

In diffuse large cell B cell lymphomas (DLBCL), B cell receptor activated B lymphocytes express large amounts of the chemokines CCL3- and CCL4. The CCL3 and CCL4 serum levels can serve as biomarkers for the prognosis of this lymphoma, since high levels are associated with a poor prognosis of this lymphoma.

TNFalpha and interleukin-1 modulate the expression of CCL3 in nucleus pulposus cells. The CCL3-CCR1 chemokine axis plays an important role in the attraction of macrophages into problabated intervertebral discs or in osteomyelitis arals.

1. Dapunt U et al (2014) The macrophage inflammatory proteins MIP1α (CCL3) and MIP2α (CXCL2) in implant-associated osteomyelitis: linking inflammation to bone degradation. Mediators Inflamm 2014:728619.
2. Soares DM et al (2009) CCL3/MIP-1 alpha is not involved in the LPS-induced fever and its pyrogenic activity depends on CRF. Brain Res 1269:54-60.
3. Takahashi K et al (2015) CCL3 and CCL4 are biomarkers for B cell receptor pathway activation and prognostic serum markers in diffuse large B cell lymphoma. Br J Haematol 171:726-735.
4. Wang J et al (2013) Tumor necrosis factor α- and interleukin-1β-dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1. Arthritis rheum 65:832-842.