Macrophage Inflammatory Proteins (MIP) belong to the family of chemotacticcytokines known as chemokines. In humans, there are two major forms, MIP-1α and MIP-1β that are now officially named CCL3 and CCL4, respectively. Both are major factors produced by macrophages after they are stimulated with bacterialendotoxins.[3] They are crucial for immune responses towards infection and inflammation.[4] They activate human granulocytes (neutrophils, eosinophils and basophils) which can lead to acute neutrophilic inflammation. They also induce the synthesis and release of other pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-α from fibroblasts and macrophages. The genes for CCL3 and CCL4 are both located on human chromosome 17.[5]
They are produced by many cells, particularly macrophages, dendritic cells, and lymphocytes.[6] MIP-1 are best known for their chemotactic and proinflammatory effects but can also promote homoeostasis.[6] Biophysical analyses and mathematical modelling has shown that MIP-1 reversibly forms a polydisperse distribution of rod-shaped polymers in solution. Polymerization buries receptor-binding sites of MIP-1, thus depolymerization mutations enhance MIP-1 to arrest monocytes onto activated human endothelium.[4]
^Czaplewski, L. G.; McKeating, J.; Craven, C. J.; Higgins, L. D.; Appay, V.; Brown, A.; Dudgeon, T.; Howard, L. A.; Meyers, T.; Owen, J.; Palan, S. R.; Tan, P.; Wilson, G.; Woods, N. R.; Heyworth, C. M.; Lord, B. I.; Brotherton, D.; Christison, R.; Craig, S.; Cribbes, S.; Edwards, R. M.; Evans, S. J.; Gilbert, R.; Morgan, P.; Randle, E.; Schofield, N.; Varley, P. G.; Fisher, J.; Waltho, J. P.; Hunter, M. G. (1999). "Identification of amino acid residues critical for aggregation of human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES. Characterization of active disaggregated chemokine variants". The Journal of Biological Chemistry. 274 (23): 16077–16084. doi:10.1074/jbc.274.23.16077. PMID10347159.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^Lodi, P. J.; Garrett, D. S.; Kuszewski, J.; Tsang, M. L.; Weatherbee, J. A.; Leonard, W. J.; Gronenborn, A. M.; Clore, G. M. (1994). "High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR". Science. 263 (5154): 1762–1767. doi:10.1126/science.8134838. PMID8134838.
