Human Lung Fibroblast Subpopulations with Different C1q Binding and Functional Properties

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Abstract
Human lung fibroblasts differing in C1q binding, steady-state levels of collagen synthesis, and other functional properties were isolated. Explants of normal human lung specimens were cultured in medium containing complement-inactivated plasma-derived human serum or complete human serum. Cells obtained were treated with C1q and fluorescein isothiocyanate-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 fibroblasts retained their respective fluorescence phenotypes after subculture. The LF fibroblasts proliferated faster than HF cells and contained more cycling cells. However, whereas the sorted HF cells grew normally, sorted LF cells grew poorly. Collagen production and pro alpha l[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 stimulated by transforming growth factor-beta and inhibited by interferon-gamma, but the stimulation was greater and inhibition less in LF cells. Our results indicate that C1q binding and the type of C1q receptors can serve as markers for fibroblast subpopulations differing in collagen synthesis, and that selection of subpopulations and their differential sensitivity to regulatory molecules can contribute to collagen alterations associated with inflammation, fibrosis, and other acquired diseases.

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