Comparative ability of human monocytes and neutrophils to degrade glomerular basement membrane in vitro

We have compared the ability of human peripheral blood monocytes and neutrophils to degrade glomerular basement membrane (GBM) in vitro. When isolated cells were incubated with GBM containing anti-GBM immune complexes, both neutrophils and monocytes adhered and spread on the surface of the GBM, underwent a respiratory burst and released lysosomal enzymes into the medium. With neutrophils, this resulted in rapid degradation of the GBM, measured both as solubilization of collagenous and noncollagenous protein. In contrast, monocytes degraded GBM very slowly, with a slight increase in the rate of hydroxyproline solubilization after approximately 24 hours incubation. Degradation of GBM by neutrophils was predominantly due to the action of serine proteinases, whereas inhibition of monocyte-mediated hydroxyproline release required both phenylmethylsulfonyl fluoride and o-phenanthroline, suggesting some synergy between serine and metalloproteinases. The results indicate that neutrophils are more able to degrade GBM components than are monocytes, and suggest that they may be capable of greater damage to the GBM in vivo, mostly due to their higher proteolytic capacity.