MIP-1α, MIP-1β

Sherry B., Franchin G.

MIP-1α and MIP-1β are members of the CC subgroup of the ehemokine family. Although these two peptides are structurally and functionally related to one another, as well as to other CC ehemokine family members, each exhibits distinct features which allows it to independently regulate specific aspects of the host inflammatory response. MIP-1α and MIP-1β clearly fall within the subset of inducible chemokines that are believed to play a pivotal role in regulating the response of the host to invading bacterial, viral, parasite, and fungal pathogens. The most well-characterized aspect of MIP-1α and MIP-1β biology is their capacity to regulate the trafficking and activation state of select subgroups of inflammatory cells (including macrophages, lymphocytes, eosinophils, dendritic cells, and NK cells). The two peptides modulate other aspects of the host inflammatory response as well, including the fever response and leukocyte adhesion to the endothelium and subsequent transmigration into the tissues. While these functions clearly contribute to the ability of the host to defend itself successfully against invading pathogens, it has been hypothesized that an overly robust MIP-1α and/or MIP-1β response can, under certain circumstances, contribute to disease-related pathophysiology. This hypothesis is supported by the fact that these two molecules, either separately or together, have been implicated in a wide range of acute and chronic inflammatory conditions including bacterial sepsis, bacterial and viral meningitis, influenza virus infection, rheumatoid arthritis, asthma, multiple sclerosis, acute and chronic respiratory diseases, allograft rejection, and central nervous system disorders.An important link between MIP-1α and MIP-1β and HIV-1 infection was revealed with the discovery that CCR5 (CC chemokine receptor which binds both MIP-1α and MIP-1β) is utilized by macrophage-tropic strains of HIV-1 as a coreceptor for entry into target cells. This discovery led to the hypothesis that the previously demonstrated antiviral actions of MlP-1α and MIP-1β resulted from their interference with virus utilization of CCR5 as a coreceptor for cell entry. In addition to these critically important inflammatory and antiviral roles, both of these molecules have been shown to regulate such normal homeostatic processes as hematopoietic cell development. lymphocyte differentiation and trafficking, immune modulation, bone remodeling, and wound healing.