CCL3, also known as macrophage inflammatory protein 1 alpha (MIP1a) and LD78, is a member of the B or CC subfamily of chemokines and is closely related to CCL4/MIP1 B. Chemokines comprise a large family of small secreted proteins that are involved in immune and inflammatory responses. CCL3 expression can be induced in a variety of hematopoietic cells, fibroblasts, smooth muscle cells, and epithelial cells. Mature canine CCL3 shares 66-67% aa sequence identity with human, mouse, and rat CCL3. CCL3 is an ~8kD chemokine that forms complexes with sulfated proteoglycans. In a reversible process, CCL3 associates into noncovalently linked dimers which then form tetramers and high molecular weight polymers. These complexes of CCL3 are protected from proteolytic digestion by insulin degrading enzyme (IDE) which can cleave the monomeric chemokine. CCL3 exerts its biological functions through interactions with CCR1, CCR3, and CCR5. It is cleared from the extracellular space by internalization via the decoy chemokine receptor D6. CCL3 promotes the chemo attraction, adhesion to activated vascular endothelium, and cellular activation of many hematopoietic cell types including activated T cells, NK cells, neutrophils, monocytes, immature dendritic cells, and eosinophils.CCL3 is also known as stem cell inhibitor (SCI) and can inhibit the proliferation of hematopoietic progenitor cells. CCL3 bioactivity contributes to tumor metastasis and the inflammatory components of viral infection, rheumatoid arthritis, and hepatitis, although it also can suppress the replication of HIV. CCL3 additionally promotes hyperalgesia by sensitizing sensory neurons to TRPV1mediated noxious stimulation.
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