Biomedical subjects

Andreas Meinhardt

Publications and source records attributed to Andreas Meinhardt.

21 records · Page 2Linked to original sources

PubMed2002

Borna disease virus-induced accumulation of macrophage migration inhibitory factor in rat brain astrocytes is associated with inhibition of macrophage infiltration.

To test the hypothesis that macrophage migration inhibitory factor (MIF) plays a role in macrophage invasion during virus-induced encephalitis, we analyzed the expression and cellular localization of MIF in the Borna disease virus (BDV)-infected rat brain, monitored monocyte/macrophage infiltration, and evaluated the influence of anti-inflammatory treatment with dexamethasone. MIF mRNA expression was restricted to neurons and remained unchanged after BDV infection or after dexamethasone treatment of either BDV-infected or uninfected control rats. In contrast, MIF protein immunoreactivity (ir) was not only seen in neurons but also in glia. After BDV-induced encephalitis and treatment of uninfected rats with dexamethasone, MIF ir was only slightly altered in neurons but moderately enhanced in tanycytes, ependyma, and choroid plexus epithelium and markedly increased or induced in astrocyte end-feet at the blood-brain barrier (BBB). The increase in MIF ir in astrocytes after BDV infection was blocked by dexamethasone. The induction or enhancement of MIF ir at the BBB significantly correlated with reduced numbers of infiltrating ED1-positive monocytes/macrophages after BDV infection. Increased macrophage invasion was observed in regions where no astrocytic MIF was detected. The BDV- or dexamethasone-induced accumulation of MIF protein in astrocytes in vivo in absence of detectable astrocytic MIF mRNA expression is most likely due to MIF translocation from neurons rather than to a constitutive or induced MIF mRNA expression in astrocytes. In conclusion, we provide evidence that translocation of MIF from neurons or other extracellular sources into astrocytes is likely to modulate the inflammatory process during the course of virus-induced encephalitis by limiting monocyte/macrophage migration through the BBB.

Animals↗

PubMed2002

Release of macrophage migration inhibitory factor and CXCL8/interleukin-8 from lung epithelial cells rendered necrotic by influenza A virus infection.

Bronchiolar epithelial cells are the prime targets for influenza A virus infection. It still remains to be clarified which signals are generated from these cells to initiate an immune response. Among chemokines, viral infection of primary lung epithelial cells triggered exclusively the release of CXCL8/interleukin-8 (IL-8), which contrasts with our previous observation that influenza A virus induced in monocytes the expression of mononuclear-leukocyte-attracting chemokines and even suppressed the production of neutrophil-attracting chemokines. Therefore, we speculated that it may be advantageous for respiratory epithelial cells to release primarily neutrophil-attracting CXCL8/IL-8 since neutrophils rapidly remove necrotic debris and are the first line of defense against bacterial superinfections. This concept has also been supported by our finding that influenza A virus infection led to necrosis of lung epithelial cells. This is in striking contrast to previous studies where influenza A virus infection induced apoptosis in monocytes and epithelial cells from origins other than the lung. Thus, the cell type instead of the virus determines which death pathway will be followed. In addition to the release of CXCL8/IL-8, we obtained a massive release of macrophage migration inhibitory factor (MIF) from virus-infected lung cells. However, whereas the CXCL8/IL-8 secretion was accompanied by induced gene activation, the transcription rate of MIF remained unchanged during the infection course and the virus-induced MIF release was predominantly a discharge from intracellular stores, suggesting that MIF is passively released upon cell death. Despite virus induced necrosis, the passively liberated MIF remained bioactive. Considering the well-established immunostimulatory effects of MIF on different leukocyte subsets, is its very likely that enhanced levels of MIF may contribute to the host immune response during the acute phase of influenza A virus infection in humans.

Cell Line↗

PubMedDate not supplied

Regulatory cytokine expression and interstitial fluid formation in the normal and inflamed rat testis are under leydig cell control.

Leydig cells have been implicated in several inflammation-related responses of the testis. Specifically, these cells produce the proinflammatory cytokines interleukin-1 (IL-1) and IL-6, stimulate macrophage recruitment, and promote interstitial fluid formation. In addition, the immunoregulatory cytokines macrophage migration inhibitory factor (MIF), transforming growth factor-beta1 (TGFbeta1), and interferon-gamma (IFNgamma) are constitutively expressed by testicular cells, including the Leydig cells. In the present study, the contribution of the Leydig cell to testicular inflammatory responses was examined in adult male rats treated with the Leydig cell-specific toxin, ethane dimethane sulfonate (EDS). Intratesticular testosterone levels were modulated by subcutaneous testosterone implants. After 10 days, animals received an injection of lipopolysaccharide (LPS) to induce an inflammatory response, or saline alone, and were killed 3 hours later. Both depletion of Leydig cells by EDS and LPS treatment caused a decrease in collected testicular interstitial fluid to about 35% of control levels, but the effects were not additive. Maintenance of intratesticular testosterone reversed the interstitial fluid decline following EDS treatment and partially prevented the LPS-induced effect. MIF, TGFbeta1, and IFNgamma were expressed in both the normal and inflamed testis at similar levels. In contrast, EDS treatment caused a significant decline in expression of all 3 cytokines, which was prevented by the testosterone implants. These data indicate that 1) expression of TGFbeta1, MIF, and IFNgamma in the testis is not dependent on the presence of intact Leydig cells but is under direct testosterone control and 2) the decline in testicular interstitial fluid during inflammation involves the Leydig cells, acting via both androgens and nonandrogenic secretions. These data provide further support for a significant role for the Leydig cell in modulating the testicular response to inflammation.

Animals↗