Crescentic glomerulonephritis is diminished in fibrinogen-deficient mice

Crescentic forms of glomerulonephritis are characterized by the accumulatio n of fibrin and cells in Bowman's space and are associated with a rapid los s of renal function. Accumulation of fibrin in the glomerular tufts is thou ght to promote macrophage infiltration and glomerular injury. To directly e xplore the role of fibrin(ogen) in the development of crescentic glomerulon ephritis, antiglomerular basement membrane nephritis was induced in fibrino gen-deficient and control mice. Glomeruli from control mice developed sever e disease including fibrin deposits, inflammatory cell accumulation, and cr escent formation (46.3 +/- 7.3% of glomeruli). Fibrinogen-deficient mice de veloped significantly milder disease with fewer glomerular crescents (24.0 +/- 4.7% of glomeruli; P < 0.03). Glomerular macrophage accumulation was di minished in fibrinogen-deficient mice (0.9 +/- 0.4 macrophages/glomerular c ross section) relative to control mice (3.9 +/- 1.4 macrophages/glomerular cross section; P < 0.03). Finally, renal function as assessed by serum crea tinine was better maintained in fibrinogen-deficient mice. These results in dicate that although fibrin( ogen) is not essential for the development of glomerular crescents, it contributes significantly to the pathogenesis of c rescentic glomerulonephritis by promoting glomerular macrophage accumulatio n and impairing filtration.