Glomerular macrophages express augmented procoagulant activity in experimental fibrin-related glomerulonephritis in rabbits.
Glomerular fibrin deposition and augmentation of procoagulant activity (PCA) are dependent on glomerular macrophage infiltration in anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) in rabbits. Expression of PCA on the surface of glomerular macrophages and/or augmentation of intrinsic glomerular cell PCA by macrophage cytokines (such as IL 1) are potential mechanisms by which macrophages may augment glomerular PCA. Macrophages were isolated from glomeruli of rabbits developing anti-GBM GN to measure their PCA expression. These macrophages were characterized by morphological and functional criteria. Glomerular macrophages expressed markedly augmented PCA (2.8 +/- 0.7 mU/10(3) cells) compared with blood monocytes (0.05 +/- 0.02 mU/10(3) cells) and alveolar macrophages (0.09 +/- 0.02 mU/10(3) cells) from the same rabbits. Glomerular macrophage PCA was functionally identical to the PCA of whole glomeruli, and was consistent with that of tissue factor. Supernatants from nephritic glomeruli contained IL 1 bioactivity and augmented endothelial cell PCA in vitro. However, these supernatants and purified IL 1 failed to augment the PCA of normal and macrophage-depleted nephritic glomeruli. These studies demonstrate that, in this model of anti-GBM GN, glomerular macrophages contribute directly to the augmented glomerular PCA by their expression of surface membrane PCA, and have the potential to indirectly augment glomerular PCA by their production of cytokines capable of enhancing endothelial cell PCA.
Tipping
P G
PG
Department of Medicine, Monash University, Melbourne, Australia.
Lowe
M G
MG
Holdsworth
S R
SR
D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism* / Q000502:physiology; D002469:Cell Separation; D002474:Cell-Free System; D005337:Fibrin; D005921:Glomerulonephritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000378:metabolism; D011650:Pulmonary Alveoli; D011817:Rabbits
D001779:Blood Coagulation Factors; C045072:macrophage procoagulant activity; D005337:Fibrin