Effects of Coal Dust and Alveolar Macrophages on Growth of Lung Fibroblasts

As a part of our study of how coal mine dusts injure the lung we have studied the effects of dusts and dust-exposed pulmonary alveolar macrophages (PAMs) on the growth of lung fibroblasts (LF). Fibroblasts were cultured near confluence in low-serum medium, either alone or in the presence of dusts, dusts plus PAMs, dust leachates or superriatants of dust-exposed PAM cultures. We report here provisional conclusions, based on initial observations. Rat LF were relatively unresponsive to direct effects of dusts, showing weak stimulation in only a few cultures, and there was no evidence that dust-exposed rat PAMs had released any growth-regulatory products. In contrast, guinea pig cells were more responsive to the dusts. The pattern of responses was quite complex. Three of the dusts stimulated LF directly (with no mediation by PAMs). Two dusts were essentially inert when added directly to fibroblast cultures, either with or without PAMs, but their leachates were active: 867 leachate was inhibitory and RF leachate was stimulatory. Dust 1361, either directly in the cultures or as an aqueous leachate, was stimulatory, and it activated cocultured PAMs to stimulate LF growth; however, supernatant products of 1361-stimulated PAMs were inhibitory. Direct exposure to 1192 stimulated LF, but its leachate was inert; cocultured PAMs exposed to 1192 had weak stimulatory effects, but supernatants of 1192-exposed PAMs were mildly inhibitory. MP3-3 had effects similar to 1192, except that the cocultured, dust-exposed PAMs had no effect on growth. We conclude 1) that guinea pig lung cells are more responsive to dusts than are rat lung cells, 2) that dusts can influence growth of LF by four kinds of interaction (by direct dust-cell interaction, by release of soluble dust components into the culture medium, by activating P AMs to exert direct cell-cell interactions, and by activating P AMs to release growth regulatory products into the culture medium), 3) that each kind of interaction may be neutral, inhibitory or stimulatory, depending on the dust tested, 4) that four of the dusts tested were neutral, inhibitory or stimulatory, depending on the assay (the fifth <lust was either neutral or stimulatory), and 5) that the effects of soluble mediators (leachates or products of activated PAMs) frequently did not correspond with the direct dust-cell or PAM-fibroblast effects. These results suggest that the nature of the dust-lung interaction at the level of cells and molecules is exceedingly complex. These observations need to be confirmed and extended to determine what characteristics of the dusts determine the nature of the cellular responses, and to determine which patterns of responses are detrimental and which are beneficial in the overall health of the dust-exposed lung.