IMMUNOHISTOCHEMICAL IDENTIFICATION AND CHARACTERIZATION OF SMOOTH MUSCLE-LIKE CELLS IN IDIOPATHIC PULMONARY FIBROSIS

The interstitium of the fibrotic lung possesses a contractile capabili ty that is unusual for nonmuscle tissue. An abundance of actin filamen t-laden cells have been demonstrated in animal and human studies of fi brotic lung tissue and have frequently been termed myofibroblasts. The origin and significance of these cells remain unclear. Proliferation of cells with the capability to contract and thereby generate force wi thin the parenchyma is potentially a significant contribution to the i ncreased lung elastic recoil of advanced pulmonary fibrosis. in the pr esent study, we immunohistochemically examined these intermediate phen otypes of filament-laden cells with a focus on those expressing smooth muscle-associated isoforms of actin. The monoclonal antibody HHF35 wa s used to study the presence and distribution of cells expressing alph a and gamma smooth muscle actin in idiopathic pulmonary fibrosis (IPF) . Adjacent sections of tissue from open lung biopsies of eight patient s with IPF were stained with a pentachrome stain and with multiple ant ibodies (HHF35, polyclonal anti-actin, anti-vimentin, anti-keratin, an ti-procollagen I, and anti-von Willebrand Factor VI II) to identify sp ecific cell types. In addition, antilaminin antibody was used to stain basement membrane. Many tightly packed, HHF35-reactive cells were fou nd to be architecturally dissociated from airways and blood vessels in all eight patients with IPF. Some HHF35-reactive bundles were compose d of loosely associated cells, and single smooth muscle cell types (SM C) were distributed in the fibrotic interstitium. Interestingly, some of the SMC were distinctly negative for anti-laminin and stained atypi cally with pentachrome. Moreover, some single SMC were found to be ant i-procollagen type I reactive with double staining technique. In summa ry, (7) abnormal collections of SMC were identified in all cases of I PF studied and (2) differential immunohistochemical staining of SMC su ggests the existence of SMC subpopulations. We speculate that these SM C clusters may contribute to tissue contraction in IPF. These study re sults demonstrating the existence of subpopulations of contractile cel ls in the lung raise further questions regarding potential phenotypic modulation or dedifferentiation of mesenchymal cells during the evolut ion of lung injury in IPF. These questions merit more extensive invest igation.