Localization of macrophage migration inhibitory factor (MIF) to secretory granules within the corticotrophic and thyrotrophic cells of the pituitary gland.

Background: Macrophage migration inhibitory factor (MIF) was one of the first lymphokine activities to be discovered and was described almost 30 years ago to be a soluble factor(s) produced by activated T lymphocytes. In more recent studies, MIF has been "rediscovered" to be an abundant, pre-formed constituent of the anterior pituitary gland and the macrophage, and to be a critical component in the host response to septic shock. Pituitary-derived MIF enters the circulation after infectious or stressful stimuli and appears to act to counterregulate glucocorticoid suppression of cytokine production.

MIF as a glucocorticoid-induced modulator of cytokine production.

Glucocorticoid hormones are important for vital functions and act to modulate inflammatory and immune responses. Yet, in contrast to other hormonal systems, no endogenous mediators have been identified that can directly counter-regulate their potent anti-inflammatory and immunosuppressive properties. Recent investigations of the protein macrophage migration inhibitory factor (MIF), which was discovered originally to be a T-lymphocyte-derived factor, have established it to be a pro-inflammatory pituitary and macrophage cytokine and a critical mediator of septic shock.

Cloning and characterization of the gene for mouse macrophage migration inhibitory factor (MIF).

An emerging body of data indicates that the protein mediator described originally as macrophage migration inhibitory factor (MIF) exerts a central and wide ranging role in host inflammatory responses. MIF is a major constituent of corticotrophic cells within the anterior pituitary gland and is secreted into the circulation in a hormone-like fashion. MIF also exists performed in monocytes/macrophages and is a pivotal mediator in the host response to endotoxic shock.

Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF).

The cytokine macrophage migration inhibitory factor (MIF) has been identified to be secreted by the pituitary gland and the monocyte/macrophage and to play an important role in endotoxic shock. Despite the recent molecular cloning of a human T-cell MIF, characterization of the biochemical and biological properties of this protein has remained incomplete because substantial quantities of purified, recombinant, or native MIF have not been available. We describe the cloning of mouse MIF from anterior pituitary cells (AtT-20) and the purification of native MIF from mouse liver by sequential ion exchange and reverse-phase chromatography.

The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor.

For over 25 years, the cytokine known as macrophage migration inhibitory factor (MIF) has been considered to be a product of activated T lymphocytes. We recently identified the murine homolog of human MIF as a protein secreted by the pituitary in response to endotoxin administration. In the course of these studies, we also detected MIF in acute sera obtained from endotoxin-treated, T cell-deficient (nude), and hypophysectomized mice, suggesting that still more cell types produce MIF.

Macrophage migration inhibitory factor is a neuroendocrine mediator of endotoxaemia.

The cytokine macrophage migration inhibitory factor (MIF) is a major protein constituent of the anterior pituitary gland released into the bloodstream during endotoxaemia. For many years, MIF had been thought to be a T cell product associated with delayed-type hypersensitivity reactions. The identification of MIF as a pituitary 'stress' hormone provides an important link in the regulation of systemic inflammatory responses by the central nervous system.

The emerging role of MIF in septic shock and infection.

The protein mediator described originally as macrophage migration inhibitory factor (MIF) has been "re-discovered" recently to be both a novel pituitary hormone and a pro-inflammatory, macrophage-derived cytokine. Emerging studies indicate that MIF plays a pivotal role not only in endotoxic shock but also in the host response to a variety of acute and chronic infections.

MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia.

Cytokines are critical in the often fatal cascade of events that cause septic shock. One regulatory system that is likely to be important in controlling inflammatory responses is the neuroendocrine axis. The pituitary, for example, is ideally situated to integrate central and peripheral stimuli, and initiates the increase in systemic glucocorticoids that accompanies host stress responses.

Leucocyte integrin and CR1 expression on peripheral blood leucocytes of patients with rheumatoid arthritis.

Expression of the leucocyte integrins (CD11a, b, c/CD18) and of CD35 (CR1) on leucocytes from the peripheral blood of patients with rheumatoid arthritis (RA) (n = 14) and control subjects (n = 12) was measured by flow cytometry using a rapid fixation and leucocyte preparation procedure. The mean (SE) percentages of lymphocytes expressing CD11a (RA 93.4 (1.

A method of preparing blood leucocytes for flow cytometry which prevents upregulation of leucocyte integrins.

LeuCAM (CD11/CD18) cell-surface antigens are easily upregulated on cell manipulation ex vivo. A procedure for preparing leucocytes, in which human blood is immediately treated ex vivo with buffered formaldehyde and then the erythrocytes and platelets are removed by lysis and differential centrifugation, has been successfully applied to the analysis of LeuCAM antigen expression by flow cytometry. We show that the increased expression of monocyte CD11/CD18, which occurs when mononuclear leucocytes are separated by a standard Lymphoprep density gradient separation, can be avoided if cells are fixed immediately.

Morphological evidence that activated polymorphs circulate in the peripheral blood of patients with rheumatoid arthritis.

Purified peripheral blood polymorphonuclear leucocytes (PMNs) from patients with rheumatoid arthritis (RA) have been found to differ from purified PMNs from normal subjects in ways that are consistent with their prior activation. However, it is currently contentious whether activated PMNs really circulate in patients with RA, or whether they are produced as an in vitro artefact of purification. Recently developed rapid leucocyte fixation and preparation technique showed that the proportion of polarised (activated) PMNs (36.

A rapid preparation technique for leucocytes.

A procedure is described for making leucocyte preparations from blood samples fixed ex vivo. Briefly, blood is treated with buffered formaldehyde and the erythrocytes and platelets removed subsequently by lysis and differential centrifugation. The fixed leucocyte preparations can then be processed or fixed further for various types of microscopy as required.