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Patterns of Lung Repair (6)

The fibroblasts are usually aligned in parallel, and immunoperoxidase staining indicates that they express smooth muscle actin but retain the intermediate filament phenotype of fibroblasts (vimentin, but no desmin) (Fig 3). The fibroblasts are enclosed by a pericellular matrix that contains fibrils of a cellular fibronectin isoform containing an extra type III homologous repeat, the EIIIA domain, not found in plasma fibronectin. The fibrils containing fibronectin are identical to structures described in healing wounds as microtendons or fibronexi, which are thought to anchor the contractile bundles of the myofibroblasts to the collagenous matrix (Fig 4).

The phenotypic features of sites of active lung fibrosis, not surprisingly, resemble healing skin wounds. The fibroblasts in healing wounds increase their collagen synthesis, produce fibronectin-incorporating sequences derived from alternatively spiced exons including the EIIIA domain, and acquire a myofibroblast morphology. As a wound begins to contract, the fibroblasts align in parallel, form well-developed contractile filament bundles, express smooth muscle actin, organize fibronectin filaments, and express high levels of the ota, p^integrin fibronectin receptor.


Figure 3. Serial sections of a fibroblastic focus in UIP. The fibroblasts express smooth muscle actin (top) but not desmin (bottom). Note that smooth muscle cells at the alveolar entrance ring express both antigens (immunoperoxidase stain X 500).


Figure 4. Electron micrograph of a fibroblast in a fibroblastic focus of UIP. An extracellular “microtendon” (mt) is stained by 5-nm gold particles conjugated to antibodies to fibronectin. The microtendon is aligned with an actin bundle (a) in the cytoplasm and collagen fibrils (at right) (X 33,000).

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