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Macrophage priming and lipopolysaccharide-triggered release of tumor necrosis factor alpha during graft-versus-host disease
| Content Provider | Semantic Scholar |
|---|---|
| Author | Nestel, Frederick P. Price, Kursteen S. Seemayer, Thomas A. Lapp, Wayne S. |
| Copyright Year | 1992 |
| Abstract | In this report we have investigated macrophage (M phi) activity and tumor necrosis factor alpha (TNF-alpha) production during graft-vs.-host disease (GVHD). TNF-alpha production by M phi requires two signals: priming of M phi by interferon followed by triggering of TNF-alpha production and release by lipopolysaccharide (LPS). The state of M phi activation was examined in nonirradiated B6AF1 recipient mice injected with either 60 x 10(6) (acute GVHD) or 30 x 10(6) (nonlethal GVHD) parental B6 lymphoid cells. During the early phase of acute GVHD, administration of normally sublethal amounts of LPS-triggered release of significant amounts of TNF-alpha into the serum resulting in death of the animals within 36 h. Normal animals treated with the same dose of LPS neither died nor produced detectable amounts of serum TNF-alpha. In vitro studies demonstrated that M phi were primed during GVHD. The level of M phi priming was greater during acute GVHD than nonlethal GVHD since 100-fold less LPS was required to trigger killing of a TNF-alpha-sensitive cell line by M phi from acute GVHD animals. The amount of TNF-alpha released into the serum after LPS injection increased during the course of the GVHD and was significantly greater in acute GVH-reactive mice. Endogenous LPS was detected in the serum of acute GVH-reactive animals coincident with the onset of mortality. The data provide evidence that during GVHD M phi are primed as a result of the allogeneic reaction and that endogenous LPS therefore triggers M phi production of TNF-alpha resulting in the symptoms characteristic of acute GVHD. |
| Starting Page | 405 |
| Ending Page | 413 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jem.rupress.org/content/jem/175/2/405.full.pdf |
| PubMed reference number | 1732411v1 |
| Volume Number | 175 |
| Journal | The Journal of experimental medicine |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acute GVH disease Adrenergic alpha-Agonists Biomarkers, Tumor Cessation of life Graft versus host disease prophylaxis/therapy Graft-vs-Host Disease Leukemia, Myelocytic, Acute Lipopolysaccharides Neoplasms Paget's Disease, Mammary Precipitating Factors Priming Exercise Transplanted tissue Tumor Necrosis Factors |
| Content Type | Text |
| Resource Type | Article |
