Macrophage inflammatory protein

Protein family

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP 1α and MIP 1β, renamed CCL3 and CCL4 respectively, since 2000. However, other names are sometimes encountered in older literature, such as LD78α, AT 464.1 and GOS19 1 for human CCL3 and AT 744, Act 2, LAG 1, HC21 and G 26 for human CCL4. Other macrophage inflammatory proteins include MIP 2, MIP 3 and MIP 5.

MIP 1α and MIP 1β are major factors produced by macrophages and monocytes after they are stimulated with bacterial endotoxin or proinflammatory cytokines such as IL 1β. CCL3 and CCL4 can bind to extracellular proteoglycans, which is not necessary for their function but it can enhance their bioactivity. The biological effect is carried out through ligation of chemokine receptors CCR1 (ligand CCL3) and CCR5 (ligands CCL3 and CCL4) and the signal is then transferred into the cell, thus these cytokines affect any cell that has these receptors. The main effect is inflammatory and mainly consists of chemotaxis and transendothelial migration but cells can be activated to release of some bioactive molecules also. These chemokines affect monocytes, T lymphocytes, dendritic cells, NK cells and platelets. and on murine chromosome 11. MIP 1 are best known for their chemotactic and proinflammatory effects but can also promote homeostasis. MIP 1δ or MIP 5 (CCL15) binds also CCR1 and CCR3.

There are two chemokines in the MIP 3 group. MIP 3α (CCL20) and MIP 3β (CCL19). CCL20 is produced by mucosa and skin by activated epithelial cells and attracts Th17 cells to the site of inflammation. It is also produced by Th17 cells themselves. It further attracts activated B cells, memory T cells and immature dendritic cells and has part in migration of these cells in secondary lymphoid organs. Mature dendritic cells down regulate CCR6 and up regulate CCR7, which is receptor for MIP 3β.

MIP 5 (sometimes called MIP 1δ) or CCL15 binds to receptors CCR1 and CCR3. It has chemotactic properties for monocytes and eosinophils and is expressed by macrophages, basophils and some tissue cells. It is proposed to have a role in pathology of asthma.