MIP (CCL3,4,9,15)

About CCL3 / MIP-1 Alpha:

Chemokine (C-C motif) ligand 3, also known as CCL3 and macrophage inflammatory protein 1-alpha is a special protein that is encoded by the CCL3 gene within humans.

Chemokines are a family of small cytokines - these are signalling proteins that come from within the cells and are secreted. The names given to these cells link to their ability to induce the process of directd chemotaxis within nearby cells. Of course, this is only works within cells that are responsive - these cells are known as chemotactic cytokines. Cytokine proteins are called chemokines due to the way in which they behave, in addition to the structural characteristics that they have in place. Also known for mediating chemotaxis, chemokines are around 8-10 kilodaltons in mass and usually have four cysteine residues kept in conserved locations, it’s these that allow them to form their three dimensional shape.

Most chemokines are a type of pro-inflamatory structure and can be used during an immune response to help bring cells to the site of an infection, to aid faster healing times. However, other chemokines are considered homeostatic and focus on controlling the migration of cells during normal processes of tissue development and maintenance. These ones are found in the vertebrates, as well as in some viruses and bacteria. However, none have been found for other invertebrates.

Chemokines are classified in four main subfamilies, these are CXC, CC, CX3C, and XC. Each of these proteins take their proteins from biological effects by interacting with g-protein linked transmembrane receptors known as chemokine receptors - these are found on the surface of target cells.

CCL3 is a cytokine belonging to the CC chemokine family, and it is a vital part of the acute inflammatory state within the process of recruitment and activation of polymorphonuclear leukocytes, simply through binding the receptors CCR1, CCR4, and CCR5.

In 1988, Sherry et al demonstrated two protein components of MIP1, called by them alpha (CCL3 protein) and beta (CCL4 protein). This gene is well expressed, 1.4 times the average rate of gene expression, to be precise. The sequence of this gene can be defined by 158 GenBank accessions from 134 cDNA clones, some from lung, placenta, blood, eye, pool germ cell tumours, and 43 other tissues.

This gene also contains 3 distinct gt-ag introns. Transcription of these gene causes four different mRNAs to be produced, three alternatively spliced variants and one unspliced form. These mRNAs seem to differ in terms of the presence or absence of a cassette exon, splicing or retention of on intron.

In terms of function, CCL3 has been tested for its association with a range of diseases. This includes HIV, abscess, acquired immunodeficiency syndrome, dementia, asthma, brain diseases, Burkitt lymphoma, burns, cellulitis, and various others. This tested association was done to determine if there was a link to participating pathways for Chagas disease, chemokine signalling pathway, cytokine-cytokine receptor interaction, T-cell polarization, and for a range of other reasons.

CCL3 can produce a monophasic fever with a rapid onset and has a magnitude that is equal or greater than that of fevers products with either recombinant human tumour necrosis factor or recombinant human interleukin-1.