The role of the macrophage in cardiac allograft rejection in the rat.
AffiliationSir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE
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AbstractMacrophages (MO) are a well-recognized component of the cellular infiltrate in first-set (acute) allograft rejections. Definition of their actual role in the mediation of rejection depends on showing that they are present in sufficient numbers and at relevant sites in rejecting grafts, that they are capable of mediating damage to graft tissues, and that their absence interfere with rejection. We have used rat heart allografts to investigate these questions. Normal rejection takes 7 days. By this time the MO is the major infiltrating cell and large numbers are present close to myocardial cells. In some cases they appear to push pseudopodia into the cell. Neither they, or other cell types, appear to be interacting with endothelial cells. MO extracted from rejecting allografts are potent secretors of plasminogen activator but show poor glass adherence and phagocytic ability compared to resident peritoneal cells. Graft MO are able to damage beating heart cells in vitro; their activity is not immunologically specific. Peritoneal MO from rats immunised with allogeneic spleen cells and MO grown in vitro from bone marrow in the absence of allostimulators behave similarly. Manipulation of MO behaviour was attempted with rabbit anti-rat MO serum. This did not prolong allograft survival and did not significantly depress blood monocyte levels. 750 rads irradiation prolonged graft survival usually until the death of the animal. Rejection could be restored with small lymphocytes from a normal rat, and the addition of bone-marrow cells had no effect. However, hearts rejected by animals given irradiation and lymphocytes alone contained as many MO as those rejected by normal animals, despite a reduction in blood monocyte levels to less than 5% of normal. We conclude that MO are present in large numbers and at relevant sites in rejecting allografts, and that they show features of activation and have a cytotoxic capability against relevant target cells. However, present approaches available for the prevention of MO accumulation in rejecting allografts are inadequate and, thus, no definitive statements about the need for MO as an effector cell in allograft rejection can be made.
CitationThe role of the macrophage in cardiac allograft rejection in the rat. 1984, 77:143-66 Immunol. Rev.
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