Distribution of laminin within rat and mouse renal, splenic, intestinal, and hepatic basement membranes identified after the intravenous injection of heterologous antilaminin IgG

Abstract

To determine the fate of circulating antibodies against the basement membrane glycoprotein laminin, affinity-purified sheep antilaminin IgG (S alpha L) was radioiodinated and intravenously injected into rats. Twenty-four hours later, approximately 60% of the bound S alpha L was present in the kidneys, spleen, small intestine, and liver and less than 1% was present within the lungs and heart. S alpha L bound rapidly to the glomerular basement membrane and reached maximal levels 75 minutes after injection. Fifteen days later, 65% of maximal levels remained within the glomerular basement membrane as shown by immunofluorescent photometry. Injected S alpha L, S alpha L that had been further purified against a pepsin-resistant subfragment of laminin (S alpha P1), and rabbit alpha L (Rb alpha L) bound in identical patterns with various basement membranes in both the rat and mouse as shown by immunofluorescent microscopy. In addition, injected conjugates of S alpha L and horseradish peroxidase (S alpha L-HRP), S alpha P1-HRP, and Rb alpha L-HRP had the same ultrastructural distribution in both rats and mice. In the kidneys, HRP reaction product was present throughout the full thickness of the glomerular basement membrane, on the base of the epithelial foot processes, and throughout the tubular basement membrane. In the spleen, alpha L was within basement membrane-like material at the periphery of the white pulp, in cords of the red pulp, and surrounding the venous sinuses. Intestinal alpha L was visualized throughout the subendothelial, crypt, and villous epithelial basement membranes and on the basal surface of the epithelium. In the liver, alpha L was present throughout the basement membranes of the portal and central veins and bile duct epithelium and on basement membrane-like structures in the space of Disse of hepatic sinusoids. Sheep, rabbits, and rats immunized against laminin did not develop antibasement membrane disease. Autoantibodies (IgG) were not detected in their basement membranes and rat alpha L injected into rats did not bind to the glomerular basement membrane. We conclude that the intravenous injection of heterologous alpha L results in the rapid deposition of alpha L within basement membranes of organs with fenestrated endothelia, laminin is present throughout basement membranes and on the surface of the epithelia adjoining basement membranes, and animals generally do not produce alpha L that binds to autologous or homologous basement membranes.