Three-dimensional collagen regulates collagen gene expression by a mechanism that requires serine/threonine kinases and is independent of mechanical contraction.

Integrin alpha1beta1, one of the cellular collagen receptors, can participate in the regulation of collagen accumulation by acting as a negative feedback regulator. The molecular mechanism behind this phenomenon has been unknown. We have plated cells inside three-dimensional collagen and analyzed a set of chemical inhibitors for various signal transduction pathways.

Antibody against human alpha 1 beta 1 integrin inhibits HeLa cell adhesion to laminin and to type I, IV, and V collagens.

In HeLa cells beta 1 integrin forms heterodimers with alpha 1, alpha 2, alpha 3, alpha 5 and alpha 6 integrin subunits. Integrin alpha v beta 5 can also be detected. A monoclonal antibody SR-84 identified the alpha 1 integrin subunit in immunoprecipitation assays and inhibited alpha 1-related cell adhesion to different matrix proteins, laminin-1 and type I, IV, and V collagens, whereas its effect on adhesion to type II collagen was marginal.

In vitro assessment of the fibrogenicity of mineral dusts.

Relying on in vitro production of the macrophage fibrogenic factor, an attempt was made to quantitate the fibrogenicity of mineral particles. Having determined the optimal conditions by means of quartz, two series of experiments were conducted with respirable coal mine dusts; the first employed artificial mixtures of a mine dust, having a low natural quartz content, with various proportions of quartz, and the second native dusts from European mines. The fibrogenic responses in both series suggest that dust concentration is more important than its composition.

Fibroblast RNA and macrophage proteins (including the fibrogenic factor) in experimental silicosis.

A hypothesis is presented for the action of silica-treated macrophages on protein synthesis in fibroblasts and also a method for the isolation of silica-attached materials in lung tissue. The increased protein synthesis in the fibroblasts is due, at least partly, to an increase in mRNA. Silica prevents the suppressing "macrophage effect" of macrophage-originated ribonuclease on fibroblasts.