XXXX -differentiated U937 cells express a macrophage-like profile of neutral proteinases. High levels of secreted collagenase and @entity2843 accompany low levels of intracellular elastase and @entity3921 .

@entity1 @entity5 @entity10757 @entity2843 @entity865 @entity3921 @entity209 @entity864
@entity1 monocytic @entity5 cells of the U937 cell line contain substantial quantities of two neutrophil neutral proteinases, elastase and @entity3921 , raising the question of whether their presence reflects an expression of transformation or whether normal monocytes undergo a developmental stage in which they produce certain neutrophil proteinases. To address this issue, we examined U937 cells for production of collagenase, since @entity1 alveolar macrophages release fibroblast-like collagenase, an enzyme that is distinct from neutrophil collagenase. Using an immunoassay that utilized antibody to skin fibroblast collagenase, we found that U937 cells secreted barely detectable quantities of enzyme, 10-12 ng/10(6) cells per 24 h, under basal conditions. Upon incubation with 10 nM @entity864 ( @entity865 ), however, collagenase release increased 200-fold, comparable to the amount secreted by @entity10757 -stimulated @entity1 fibroblasts. @entity209 and immunoprecipitation confirmed the enhanced synthesis of U937 cell collagenase upon @entity865 exposure. This enzyme activity further resembled fibroblast collagenase and differed from neutrophil collagenase by exhibiting preferential cleavage of monomeric type III collagen relative to type I. As previously observed with @entity1 alveolar macrophages, U937 cells also released a protein identical to the @entity2843 produced by @entity1 skin fibroblasts, a molecule not associated with neutrophils. Release of this inhibitor increased 10-fold with @entity865 exposure. In contrast to collagenase and collagense inhibitor, @entity865 -treated U937 cells contained only 10-15% as much elastase and @entity3921 activities as control cells. Thus, @entity865 -induced differentiation modified the presence of these enzymes in the direction of their content in normal monocytes. Since the neutral proteinase profile of undifferentiated U937 cells resembles that of neutrophils and changes markedly after cellular differentiation to one that is characteristic of monocytes, these data suggest that neutrophilic proteinases may be produced by normal monocytes during the early stages of their differentiation.
