Monocyte chemoattractant protein-1 and RANTES are chemotactic for graft infiltrating lymphocytes during acute lung allograft rejection

Graft infiltrating lymphocytes (GILs) are crucial to rejection of lung allo grafts. However, chemotactic activities, chemokines responsible for GIL rec ruitment, and cells involved in chemokine production during lung allograft rejection have not been evaluated. This study determined whether chemotacti c activity for GILs is upregulated, and whether the chemokines monocyte che moattractant. protein (MCP)-1 and regulated on activation, normal T cells e xpressed and secreted (RANTES) have roles in GIL chemotaxis during lung all ograft rejection. F344 (RT1(lV1)) rat lung allografts were transplanted int o WKY (RT1(l)) recipients. Chemotactic activity for GILs and quantities of MCP-1 and RANTES were determined in allograft bronchoalveolar lavage fluid 1 wk after transplantation. Data showed that during rejection, chemotactic activity for GILs is upregulated, MCP-1 and RANTES are produced locally, an d both MCP-1 and RANTES are operative in GIL recruitment. Immunohistochemis try showed that alveolar macrophages (AMs) were the major source of MCP-1 a nd that other lung cells, including AMs, were the source of RANTES. Further , depletion of AMs in the donor lung before transplantation downregulated c hemotaxis for GILs and production of MCP-1 during rejection episodes. These data show that chemotaxis for GILs is upregulated locally during lung allo graft rejection, and that MCP-1 and RANTES contribute to GIL recruitment du ring the rejection response.