Thy1 (+) and (-) lung fibrosis subpopulations in LEW and F344 rats

Abstract

Appreciation of the potential of fibroblasts as effector cells in inflammation has led to the recognition of fibroblast subpopulations, the most stable of which are the Thy1 (+) and Thy1 (-) subpopulations in mouse lung fibroblasts. We investigated the presence of Thy1 (+) and (-) fibroblasts in rats, comparing the percentage in primary cultures from rats with different susceptibility to fibrosis, and whether the characteristics were similar in mice and rats, and between normal and fibrotic rats lungs. Using primary cultures of rat fibroblasts obtained both from normal and fibrotic lungs, we analysed the percentage of Thy1 (+) and (-) fibroblasts by fluorescence-activated cell sorter (FACS) analysis. We sorted the fibroblasts to evaluate immune region associated antigen (Ia) expression, which tends to be raised in tissues involved in inflammation, and other characteristics. We found that Thy1 (+) and (-) fibroblasts: 1) are distinct subpopulations in rat lungs; 2) are found in different proportions in rat strains with different propensity towards lung fibrosis; and 3) have similar but not identical characteristics in mice and rats. We also found that bleomycin-induced fibrosis increases the percentage of Ia expression in Thy1 (-), but not Thy1 (+) fibroblasts. The presence of these stable fibroblast supopulations in multiple species, and the fact that these fibroblasts differ in their response to a fibrosing agent, suggests the importance of considering fibroblast subpopulations in development and disease.