Absence Of Mononuclear Cells Research Articles

Macrophage migration inhibitory factor inhibits neutrophil apoptosis by inducing cytokine release from mononuclear cells.

The chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) is a pivotal driver of acute and chronic inflammatory conditions, cardiovascular disease, autoimmunity, and cancer. MIF modulates the early inflammatory response through various mechanisms, including regulation of neutrophil recruitment and fate, but the mechanisms and the role of the more recently described MIF homolog MIF-2 (D-dopachrome tautomerase; D-DT) are incompletely understood. Here, we show that both MIF and MIF-2/D-DT inhibit neutrophil apoptosis. This is not a direct effect, but involves the activation of mononuclear cells, which secrete CXCL8 and other prosurvival mediators to promote neutrophil survival. Individually, CXCL8 and MIF (or MIF-2) did not significantly inhibit neutrophil apoptosis, but in combination they elicited a synergistic response, promoting neutrophil survival even in the absence of mononuclear cells. The use of receptor-specific inhibitors provided evidence for a causal role of the noncognate MIF receptor CXCR2 expressed on both monocytes and neutrophils in MIF-mediated neutrophil survival. We suggest that the ability to inhibit neutrophil apoptosis contributes to the proinflammatory role ascribed to MIF, and propose that blocking the interaction between MIF and CXCR2 could be an important anti-inflammatory strategy in the early inflammatory response.

Macrolide antibiotics directly reduce active oxygen generation by neutrophils in human peripheral blood.

Since a "low-dose and long-term" administration of erythromycin (EM) was reported to be effective in patients with chronic respiratory diseases, including diffuse panbronchiolitis (DPB), the modulation of host defense responses by EM has attracted much attention. Despite considerable controversy, it was recently demonstrated that macrolides reduced neutrophil function. In this study, we investigated the effects of EM, a 14-membered ring macrolide, azithromycin (AZM), a 15-membered ring macrolide, and rokitamycin (RKM), a 16-membered ring macrolide, on neutrophil function in terms of active oxygen generation of neutrophils in the absence and presence of mononuclear cells in vitro. EM and AZM significantly suppressed active oxygen generation by neutrophils in the absence of mononuclear cells at low concentration (0.5 microgram/ml. p < 0.05). At the next step, to confirm that EM and AZM directly reduced active oxygen generation by neutrophils, we investigated whether mononuclear cells affected this effect of EM and AZM. In the presence of mononuclear cells pretreated with EM or AZM, both antibiotics suppressed active oxygen generation at concentrations ranging from 0.5 to 20 micrograms/ml. However, the inhibition rates induced by EM and AZM at low concentrations were not so different between the absence and the presence of mononuclear cells. These results indicated that EM and AZM have direct effects on the active oxygen generation by neutrophils and those effects that were not influenced by mononuclear cells. This inhibitory effect may be responsible for the therapeutic efficacy of these 14-membered and 15-membered ring macrolides in patients with DPB.

The action of Guillain-Barré syndrome serum on myelin: A tissue culture and electron microscopic analysis

In the early phase of the Guillain-Barré syndrome, a factor in serum which is active on myelinated fibres in vitro may be detected; this factor was found in 5 out of 6 cases and was complement-dependent and not cytotoxic in 4 cases. Myelin swellings appeared in the living spinal ganglia cultures 4 days after exposure to activated GBS sera; the myelinated fibres were further fragmented into large ovoids or in refringent spheres apparently located in the Schwann cell. On electron microscopy, primary myelin alterations with axonal preservation consisted of a marked oedema with splitting of myelin at the intraperiodic line, lamellar disintegration and alterations of internal Schwann cell cytoplasm. Wallerian degeneration was also observed in some fibres. The perinuclear cytoplasm of the myelin supporting cell and its plasma membrane were well-preserved and at the same time that myelin breakdown took place in some fibres, contact between the axon and Schwann cell surface with subsequent membrane synthesis seemed to remain possible in others. The lesions obtained in vitro with some GBS sera, in the absence of mononuclear cells, have thus some similarities with those observed in the nerve fibres in vivo but the precise role of this serum factor in cases of this disease remains to be elucidated.