The role of macrophage migration inhibitory factor in endotoxin shock

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Macrophage migration inhibitory factor (MIF) was the first lymphokine discovered in lectin-activated T lymphocytes. It was originally identified by its ability to prevent the migration of macrophages out of a capillary tube in vitro. Human MIF cDNA was first cloned from T-lymphocytes, which revealed that the protein consists of 114 amino acid residues. MIF has long been considered to be expressed exclusively in activated T-lymphocytes ; however, a recent report indicated that macrophages are another majorsource of MIF.Various novel biological properties of MIF have been discovered. MIF is the major secretory protein released by anterior pituitary cells in response to lipopolysaccharide stimulation and is considered to play a central role in endotoxemia.During the course of our MIF study, we cloned rat MIF cDNA, and reported its physicochemical properties. We moreover succeeded in the crystallization of both human and rat MIFs, and elucidated the tertiary structure of rat MIF at 2.2 A resolution. Furthermore, we identified the expression of MIF in human skin and cornea, which indicated that expression of MIF was not limited to T lymphocytes and macrophages.