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Biomedical subjects

K Lemström

Publications and source records attributed to K Lemström.

At least 37 records · Page 2Linked to original sources
PubMed1994

Acute cytomegalovirus infection induces a subendothelial inflammation (endothelialitis) in the allograft vascular wall. A possible linkage with enhanced allograft arteriosclerosis.

Clinical and experimental studies have established the accelerating role of cytomegalovirus (CMV) infection on cardiac allograft arteriosclerosis, ie, chronic rejection. We have investigated the mechanisms behind the interaction between CMV infection and chronic rejection. In the first part of the study, 762 endomyocardial biopsy specimens obtained from 47 heart allograft recipients were analyzed. Of these, 28 patients developed CMV infection during the first postoperative year. In 24 of 28 CMV patients, mononuclear inflammatory cells (endothelialitis) were seen in the subendothelium of small intramyocardial arterioles. In CMV-free recipients, only five of 19 had any subendothelial inflammation in the vascular structures P < 0.0001 when compared with CMV patients). The subendothelial inflammation demonstrated an intensive peak at the onset of CMV infection, subsiding slowly thereafter. Morphologically, the inflammatory cells in the subendothelium were small lymphocytes. Only few activated pyroninophilic lymphocytes were seen. Immunohistochemistry revealed that the lymphocytes were mostly T cells (UCHL1+). In the second part of the study, we investigated if a similar endothelialitis could be induced experimentally in allografted rats. We performed rat aortic allografts from the DA (AG-B4, RT1a) donors to the WF (AG-B2, RT1v) recipients and infected the recipients with 10(5) plaque-forming units of rat CMV Maastricht strain 1 day after transplantation. In rat CMV-infected aortic allografts, the frequency of subendothelial leukocyte common antigen (LCA, OX1) positive leukocytes, 1.7 +/- 0.1 (SEM) point score units, was significantly higher when compared to noninfected allografts, 0.8 +/- 0.1 point score units (P < 0.05), and they were most prominent in the intimal space during and following acute infection. During subsequent weeks, the LCA-positive leukocytes were replaced by alpha-actin-positive smooth muscle cells. Instead, most of the cells in intima of CMV-free grafted rats stained positively to alpha-actin from the beginning and were smooth muscle cells. Practically no leukocytes were seen. In rat CMV-infected aortic allografts most subendothelial inflammatory cells represented T cells (W3/25+) and cells of the monocyte/macrophage lineage (OX42+). In conclusion, acute CMV infection is associated with an subendothelial inflammation (endothelialitis) of allograft vascular structures both in human and in rat. Nonactivated T lymphocytes and monocytes predominate the inflammatory lesion in the subendothelium. The results suggest that the virus-linked vascular wall inflammation may play a role in the immune injury toward allograft vascular structures, particularly to endothelium, and thus contribute to allograft arteriosclerosis.

Acute Disease↗
PubMed1992

Towards understanding the pathophysiology of chronic rejection.

Chronic allograft rejection is the major reason why allografts are lost. While only 2%-3% of all allografts are lost during the first year to irreversible acute rejection, approximately 6%-7% are lost during each subsequent year to chronic rejection. The major manifestation of chronic rejection in all organs is persistent perivascular inflammation and allograft arteriosclerosis. Bearing this in mind, we have developed a model to investigate the pathophysiology of allograft arteriosclerosis using aortic transplantations between inbred rat strains. The results obtained thus far indicate that several different inflammatory cascades are operative within the vascular wall during allograft arteriosclerosis. The relative importance of these different cascades, and particularly the role of growth factors as final effectors, has not yet been defined. Attempts to suppress allograft arteriosclerosis under experimental conditions have already met with some success: under conditions where no immunosuppression is provided we have been able to delay the process by at least 3 months, though we have not been able to block it indefinitely. It may be expected, however, that once the inflammatory cascades leading to smooth muscle cell replication in the allograft media and their influx into the intima are better defined, more specific approaches to the inhibition of allograft arteriosclerosis will be developed.

Animals↗