GLOMERULAR TISSUE FACTOR EXPRESSION IN CRESCENTIC GLOMERULONEPHRITIS - CORRELATIONS BETWEEN ANTIGEN, ACTIVITY, AND MESSENGER-RNA

Correlations between glomerular expression of tissue factor (TF) activ ity and antigen and cellular localization of TF mRNA was studied in cr escentic glomerulonephritis (GN) in rabbits. Glomerular TF activity in creased 8.7-fold 24 hours after initiation of GN (234 +/- 49 mU/10(3) glomeruli; normal, 27 +/- 10 mU/10(3) glomeruli; P = 0.003) in associa tion with a 2.1-fold increase in TF antigen (154 +/- 34 ng/10(3) glome ruli; normal, 72 +/- 10 ng/10(3) glomeruli; P = 0.055), early macropha ge infiltration, and no significant increase in TF mRNA. At the peak g lomerular macrophage infiltration (day 4), TF activity remained augmen ted (230 +/- 63 mU/10(3) glomeruli) and TF mRNA, colocalized within ma crophages, was significantly increased compared with normal (267 +/- 4 2%; P = 0.001). TF antigen was not increased in glomeruli (114 +/- 17 ng/10(3) glomeruli), although significant urinary excretion of TF anti gen was detectable (478 +/- 121 ng/24 hours; normal, <1 ng/24 hours; P = 0.032). At this time, the M(r) of glomerular TF (49 to 61 kd) was i ncreased compared with TF in normal glomeruli (49 to 58 kd) as a resul t of increased glycosylation. At day 7, TF activity and antigen within glomeruli had decreased, although urinary excretion of TF antigen and glomerular TF mRNA remained elevated. These studies suggest that earl y up-regulation of TF activity is largely a result of functional up-re gulation of constitutive TF in intrinsic glomerular cells. In more adv anced disease, infiltrating macrophages are the major site of TF synth esis. The increased M(r) of glomerular TF, as a result of synthesis of more highly glycosylated protein by macrophages and the shedding of T F into the urine, suggests that substantial turnover of glomerular TF occurs at this stage.