Am. J. Respir. Cell Mol. Biol., Volume 23, Number 6, December, 2000 719-726

Monocyte Chemoattractant Protein-1 and RANTES Are Chemotactic for Graft Infiltrating Lymphocytes during Acute Lung Allograft Rejection

Yasuo Sekine, Kazuhiro Yasufuku, Kathleen M. Heidler, Oscar W. Cummings, Nico Van Rooijen, Takehiko Fujisawa, John Brown, and David S. Wilkes

Departments of Medicine, Microbiology and Immunology, Pathology, and Surgery, Indiana University School of Medicine, Indianapolis, Indiana; Department of Surgery, Institute of Pulmonary Cancer Research, Chiba University School of Medicine, Chiba, Japan; and Department of Cell Biology and Immunology, Faculty of Medicine, Vrije University, Amsterdam, The Netherlands

Graft infiltrating lymphocytes (GILs) are crucial to rejection of lung allografts. However, chemotactic activities, chemokines responsible for GIL recruitment, and cells involved in chemokine production during lung allograft rejection have not been evaluated. This study determined whether chemotactic activity for GILs is upregulated, and whether the chemokines monocyte chemoattractant protein (MCP)-1 and regulated on activation, normal T cells expressed and secreted (RANTES) have roles in GIL chemotaxis during lung allograft rejection. F344 (RT1^lv1) rat lung allografts were transplanted into 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, and both MCP-1 and RANTES are operative in GIL recruitment. Immunohistochemistry showed that alveolar macrophages (AMs) were the major source of MCP-1 and that other lung cells, including AMs, were the source of RANTES. Further, depletion of AMs in the donor lung before transplantation downregulated chemotaxis for GILs and production of MCP-1 during rejection episodes. These data show that chemotaxis for GILs is upregulated locally during lung allograft rejection, and that MCP-1 and RANTES contribute to GIL recruitment during the rejection response.

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