Using a rat air pouch model of red cell promoted allergic inflammation, we have investigated the relation between ferritin synthesis and iron deposition in pouch wall lining cells. These cells have structural and immunohistochemical similarities to human synovial intimal cells and studies of them are pertinent to the clinical situation. In control air pouch wall tissue after single or double antigenic challenge the (apo)ferritin containing macrophages are most numerous seven days after antigenic challenge when there is active connective tissue proliferation and a generalised mononuclear cell response in the pouch wall, suggesting that (apo)ferritin is produced in macrophages as part of the tissue inflammatory response. In contrast with control tissue, where there is a steady decrease in positive cells over the ensuing weeks, injection of blood into both single and double challenge air pouches produces a significant (p less than 0.001) and continuing rise in the numbers of ferritin containing macrophages after day 7. Also, after 14 days Perls' positive ferric iron is detectable in increasing numbers of ferritin containing macrophages, a trend which is more marked in double challenge, blood injected air pouches. The histological data clearly show that there is a close relation between the presence of Perls' iron and proliferation of vascular and connective tissue elements in the pouch wall. We propose that this proinflammatory role of iron is the result of its ability to promote oxidative damage in tissues, and discuss ways in which this may take place.
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