Reprint requests to: Dr. E. von Willebrand Transplantation Laboratory University of Helsinki PO Box 21 (Haartmaninkztu 3) SF 00014 Helsinki, Finland
Supported by the Finnish Academy of Science.
Normal kidneys and stable grafts express varying amounts of adhesion molecules on endothelial cells of capillaries and larger vessels [4-6].The relationship between ICAM-1 and Class II induction in acute rejection of renal transplants has been demonstrated previously [7, 8], but the relationship between other adhesion molecule and activation marker induction has not been studied. The expression of cellular adhesion molecules; intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), platelet endothelial cell adhesion molecule (PECAM-1) is regulated by several cytokines, which are produced early during lymphoid and monocytic activation [1-3]
We have studied the induction of lymphoid activation markers CD25 (IL2 receptors), CD69 (AIM, early lymphoid activation), HLA ClassII molecules and the monocytic marker CD68 and their relationship to the expression of cellular adhesion molecules; intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet-endothelial cell adhesion molecule-1 (PECAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1), in renal transplants with acute rejection and compared the findings to transplants with no rejection.
In the 10 grafts with no rejection, there were no interstitial infiltrates, CD2 lymphocytes low 3 ±3, and no induction of lymphoid activation markers, no IL2-receptors and no CD69 lymphocytes. Also monocytes and ClassII positive cells were low, 4 ±3 and 9 ±9, respectively per high power visual field. ICAM-1, VCAM-1 and PECAM-1 expressing cells were low: 13 ±10, 16 ±13, 16 ±13. ELAM-1 expression was very low, 1 ±1. The differences between the two groups were all statistically significant, p. <0.005.
The major target of acute rejection in kidney allografts, is the vascular endothelium, especially of the intertubular capillaries. The expression of vascular adhesion molecules on the cell membrane are involved with the early phase of lymphoid activation and serve as adhesion receptors for lymphocytes and other inflammatory cells . Cellular adhesion molecules and their ligands also have an important role in leucocyte extravasation and in the development of cellular infiltrates in different tissues, also in transplants. This study demonstrates, that in acute rejection molecular activation markers are induced on infiltrating inflammatory cells and are related to a strong induction of adhesion molecules on different components of the kidney graft, and that these phenomena can be used in rejection diagnosis.
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Table 1: Activation markers and adhesion molecules in rejection diagnosis.
|NOR||3 ±3||0 ±0||0 ±0||4 ±3||9 ±9||13 ±10||16 ±13||16 ±13||1 ±1|
|REJ||40 ±23*||12 ±5*||5 ±4*||70 ±8*||60 ±41*||97 ±20*||80 ±38*||69 ±16*||12 ±9*|
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