HUMAN LUNG FIBROBLAST SUBPOPULATIONS WITH DIFFERENT C1Q BINDING AND FUNCTIONAL-PROPERTIES

Human lung fibroblasts differing in C1q binding, steady-state levels o f collagen synthesis, and other functional properties were isolated. E xplants of normal human lung specimens were cultured in medium contain ing complement-inactivated plasma-derived human serum or complete huma n serum. Cells obtained were treated with C1q and fluorescein isothioc yanate-anti-C1q antibody and separated based on fluorescence intensity in a fluorescence-activated cell sorter (FACS). FACS profiles showed that fibroblasts obtained in the presence of plasma-derived serum (HF cells) displayed higher fluorescence intensity than those obtained in complete serum (LF cells). The unsorted and sorted HF and LF fibroblas ts retained their respective fluorescence phenotypes after subculture. The LF fibroblasts proliferated faster than HF cells and contained mo re cycling cells. However, whereas the sorted HF cells grew normally, sorted LF cells grew poorly. Collagen production and pro-alpha[I] mRNA levels in HF cells were 2.6 +/- 0.7 and 2.1 +/- 0.6 times as high as LF cells (n = 4). Collagen synthesis in both HF and LF cells was stimu lated by transforming growth factor-beta and inhibited by interferon-g amma, but the stimulation was greater and inhibition less in LF cells. Our results indicate that C1q binding and the type of C1q receptors c an serve as markers for fibroblast subpopulations differing in collage n synthesis, and that selection of subpopulations and their differenti al sensitivity to regulatory molecules can contribute to collagen alte rations associated with inflammation, fibrosis, and other acquired dis eases.