Expression of allograft inflammatory factor-1 in T lymphocytes: a role in T-lymphocyte activation and proliferative arteriopathies.
Allograft inflammatory factor (AIF)-1 is a cytoplasmic, calcium-binding protein whose expression in transplanted human hearts correlates with rejection and development of coronary artery vasculopathy (CAV). AIF-1 is constitutively expressed in monocytes/macrophages, but its expression in human lymphocytes has not been described. After immunohistochemical analysis of human coronary arteries with CAV, we identified AIF-1 expression in CD3-positive lymphocytes. AIF-1 was differentially expressed in peripheral blood mononuclear cells and in the T-lymphoblastoid MOLT-4 cell line exposed to various cytokines, suggesting a role for AIF-1 in T-lymphocyte activation. To determine AIF-1 function, MOLT-4 cells were stably transduced by AIF-1 retrovirus. Overexpression of AIF-1 in these cells led to a 238% increase in cell number compared to empty vector controls. AIF-1 polymerized nonmuscle actin and MOLT-4 cells overexpressing AIF-1 migrated 95% more rapidly than empty vector controls. Primary human vascular smooth muscle cells cultured in conditioned media from AIF-1-transduced MOLT-4 cells proliferated 99% more rapidly than vascular smooth muscle cells cultured in conditioned media from empty vector-transduced MOLT-4 cells. These data indicate that AIF-1 is expressed in activated T lymphocytes, that its expression enhances activation of lymphocytes, and that AIF-1 expression in activated lymphocytes may have important ramifications for activation of adjacent arterial vascular smooth muscle cells and development of CAV.
Kelemen
Sheri E
SE
Department of Cardiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia PA 19140, USA.
Autieri
Michael V
MV
D000199:Actins / Q000378:metabolism; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism; D008840:Microfilament Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism*
C112986:AIF1 protein, human; D000199:Actins; D002135:Calcium-Binding Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins