This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tipping, P. G. Articles by Holdsworth, S. R. Search for Related Content PubMed PubMed Citation Articles by Tipping, P. G. Articles by Holdsworth, S. R.

American Journal of Pathology, Vol 147, 1736-1748, Copyright © 1995 by American Society for Investigative Pathology

REGULAR ARTICLES

Glomerular tissue factor expression in crescentic glomerulonephritis. Correlations between antigen, activity, and mRNA

PG Tipping, JH Erlich, J Apostolopoulos, N Mackman, D Loskutoff and SR Holdsworth
Department of Medicine, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.

Correlations between glomerular expression of tissue factor (TF) activity and antigen and cellular localization of TF mRNA was studied in crescentic glomerulonephritis (GN) in rabbits. Glomerular TF activity increased 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 association with a 2.1-fold increase in TF antigen (154 +/- 34 ng/10(3) glomeruli; normal, 72 +/- 10 ng/10(3) glomeruli; P = 0.055), early macrophage infiltration, and no significant increase in TF mRNA. At the peak glomerular macrophage infiltration (day 4), TF activity remained augmented (230 +/- 63 mU/10(3) glomeruli) and TF mRNA, colocalized within macrophages, was significantly increased compared with normal (267 +/- 42%; P = 0.001). TF antigen was not increased in glomeruli (114 +/- 17 ng/10(3) glomeruli), although significant urinary excretion of TF antigen 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 increased compared with TF in normal glomeruli (49 to 58 kd) as a result 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 early up-regulation of TF activity is largely a result of functional up-regulation of constitutive TF in intrinsic glomerular cells. In more advanced disease, infiltrating macrophages are the major site of TF synthesis. The increased M(r) of glomerular TF, as a result of synthesis of more highly glycosylated protein by macrophages and the shedding of TF into the urine, suggests that substantial turnover of glomerular TF occurs at this stage.

This article has been cited by other articles:

				B. Naumnik, J. Borawski, L. Chyczewski, K. Pawlak, and M. Mysliwiec Tissue factor and its inhibitor in human non-crescentic glomerulonephritis--immunostaining vs plasma and urinary levels Nephrol. Dial. Transplant., December 1, 2006; 21(12): 3450 - 3457. [Abstract] [Full Text] [PDF]

				C. Xi, X. Chen, X. Sun, S. Shi, Z. Feng, J. Wang, Q. Hong, Y. Lu, and S. Lin Effects of Alterations of Glomerular Fibrin Deposition on Renal Inflammation in Rats at Different Age Stages J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2005; 60(9): 1099 - 1110. [Abstract] [Full Text] [PDF]

				N. Liu, T. Makino, F. Nogaki, H. Kusano, K. Suyama, E. Muso, G. Honda, T. Kita, and T. Ono Coagulation in the mesangial area promotes ECM accumulation through factor V expression in MsPGN in rats Am J Physiol Renal Physiol, October 1, 2004; 287(4): F612 - F620. [Abstract] [Full Text] [PDF]

				A. Hertig and E. Rondeau Role of the Coagulation/Fibrinolysis System in Fibrin-Associated Glomerular Injury J. Am. Soc. Nephrol., April 1, 2004; 15(4): 844 - 853. [Abstract] [Full Text] [PDF]

				J. R. Timoshanko, J. D. Sedgwick, S. R. Holdsworth, and P. G. Tipping Intrinsic Renal Cells Are the Major Source of Tumor Necrosis Factor Contributing to Renal Injury in Murine Crescentic Glomerulonephritis J. Am. Soc. Nephrol., July 1, 2003; 14(7): 1785 - 1793. [Abstract] [Full Text] [PDF]

				A. J. Chong, T. H. Pohlman, C. R. Hampton, A. Shimamoto, N. Mackman, and E. D. Verrier Tissue factor and thrombin mediate myocardial ischemia-reperfusion injury Ann. Thorac. Surg., February 1, 2003; 75(2): S649 - 655. [Abstract] [Full Text] [PDF]

				K. E. WELTY-WOLF, M. S. CARRAWAY, D. L. MILLER, T. L. ORTEL, M. EZBAN, A. J. GHIO, S. IDELL, and C. A. PIANTADOSI Coagulation Blockade Prevents Sepsis-induced Respiratory and Renal Failure in Baboons Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1988 - 1996. [Abstract] [Full Text] [PDF]

				M. G. Robson, H. T. Cook, M. Botto, P. R. Taylor, N. Busso, R. Salvi, C. D. Pusey, M. J. Walport, and K. A. Davies Accelerated Nephrotoxic Nephritis Is Exacerbated in C1q-Deficient Mice J. Immunol., June 1, 2001; 166(11): 6820 - 6828. [Abstract] [Full Text] [PDF]

				J. H. Erlich, E. M. Boyle, J. Labriola, J. C. Kovacich, R. A. Santucci, C. Fearns, E. N. Morgan, W. Yun, T. Luther, O. Kojikawa, et al. Inhibition of the Tissue Factor-Thrombin Pathway Limits Infarct Size after Myocardial Ischemia-Reperfusion Injury by Reducing Inflammation Am. J. Pathol., December 1, 2000; 157(6): 1849 - 1862. [Abstract] [Full Text] [PDF]

				B. A. Lwaleed Is tissue factor a mediator of fibrin deposition in glomerular pathology? Nephrol. Dial. Transplant., October 1, 1999; 14(10): 2533 - 2533. [Full Text] [PDF]

				J. Erlich, G. C. N. Parry, C. Fearns, M. Muller, P. Carmeliet, T. Luther, and N. Mackman Tissue factor is required for uterine hemostasis and maintenance of the placental labyrinth during gestation PNAS, July 6, 1999; 96(14): 8138 - 8143. [Abstract] [Full Text] [PDF]

				J. Erlich, C. Fearns, J. Mathison, R. J. Ulevitch, and N. Mackman Lipopolysaccharide Induction of Tissue Factor Expression in Rabbits Infect. Immun., May 1, 1999; 67(5): 2540 - 2546. [Abstract] [Full Text] [PDF]

				M. A. CUNNINGHAM, X. R. HUANG, J. P. DOWLING, P. G. TIPPING, and S. R. HOLDSWORTH Prominence of Cell-Mediated Immunity Effectors in "Pauci-Immune" Glomerulonephritis J. Am. Soc. Nephrol., March 1, 1999; 10(3): 499 - 506. [Abstract] [Full Text]

				A. R. Kitching, S. R. Holdsworth, V. A. Ploplis, E. F. Plow, D. Collen, P. Carmeliet, and P. G. Tipping Plasminogen and Plasminogen Activators Protect against Renal Injury in Crescentic Glomerulonephritis J. Exp. Med., March 3, 1997; 185(5): 963 - 968. [Abstract] [Full Text] [PDF]

				A. F. Drew, H. L. Tucker, H. Liu, D. P. Witte, J. L. Degen, and P. G. Tipping Crescentic glomerulonephritis is diminished in fibrinogen-deficient mice Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1157 - F1163. [Abstract] [Full Text] [PDF]