Morphologic and functional characteristics of subpopulations of murine lung fibroblasts grown in vitro.

Fibrotic development is a common response of the lung to toxic or deleterious insult. For example, the lung is the dose-limiting organ for irradiation of the thorax for primary or metastatic lesions, due in large part to latent fibrosis. The development of the fibrotic response reflects a cascade of cell-cell and cell-extracellular matrix interactions, the ultimate target of which is the fibroblast. There is increasing evidence of subpopulations of pulmonary fibroblasts, which may have differing roles in either the initiation or progression of fibrosis. Recently we described two fibroblast subpopulations from the murine lung, which differ in the presence or absence of the membrane antigen Thy-1 (Phipps et al., 1989). These Thy-1+ and Thy-1- subpopulations are stable and differ in certain functions, such as the production of cytokines and the display of Class II MHC antigens. To determine the morphologic development of the two subpopulations and their growth characteristics in vitro, cultures of the two cell subtypes were prepared for transmission and scanning electron microscopy at varying stages of growth. Thy-1+ fibroblasts are more spindle-shaped, contain intracellular lipid, exhibit abundant cell-cell contacts, and are capable of secreting large amounts of collagen and modest amounts of fibronectin. Thy-1- fibroblasts are more rounded and spread, contain no intracellular lipid droplets, possess more intracellular microfilaments and microtubules, and synthesize less collagen and more fibronectin than do Thy-1+ cells. There are no significant differences between the two subpopulations insofar as growth rates are concerned, but Thy-1+ fibroblasts possess an additional DNA peak during periods of early growth.