Cloning and characterization of allograft inflammatory factor-1: a novel macrophage factor identified in rat cardiac allografts with chronic rejection

Abstract

The development of arteriosclerotic lesions in the Lewis to F344 rat model of chronic cardiac rejection is characterized by macrophage adhesion to the vessel lumen and macrophage infiltration in the neointima prior to smooth muscle cell accumulation. We report the cloning and characterization of allograft inflammatory factor-1 (AIF-1), a novel cDNA that is expressed early and persistently in chronically rejecting cardiac allografts but is absent in cardiac syngrafts and host hearts. The full-length cDNA codes for a hydrophilic polypeptide of 17 kD that contains a 12-amino acid region similar to an EF-hand (calcium-binding) domain. In cardiac allografts AIF-1 transcripts and protein localized to infiltrating mononuclear cells. Analysis of isolated cell populations confirmed that AIF-1 was selectively expressed in macrophages and neutrophils and demonstrated that AIF-1 transcripts could be upregulated by sixfold after stimulation with the T cell-derived cytokine IFN-gamma. Treatment with a diet deficient in essential fatty acids (which attenuates arteriosclerosis) or CTLA-4 Ig (which blocks lymphocyte activation) significantly decreased AIF-1 transcript levels. Upregulation of AIF-1 in the setting of T cell activation suggests that it may play a role in macrophage activation and function.