Studies of Bronchoalveolar Lavage Cells and Fluids in Pulmonary Sarcoidosis: II. Enhanced Capacity of Bronchoalveolar Lavage Fluids from Patients with Pulmonary Sarcoidosis to Induce Cell MovementIn Vitro

Abstract

The ability to increase the motility of endothelial cells in vitro is a property common to most if not all angiogenesis-inducing factors. Because bronchoalveolar lavage (BAL) cells from patients with pulmonary sarcoidosis have an enhanced capacity to induce neovascularization, the BAL fluids from these patients were assessed for their effect on human and murine endothelial cells and fibroblasts obtained from a variety of tissue sources. A recently developed computer-assisted image analysis system was used to determine the extent and pattern of cell migration in a microwell screening assay. Data were obtained for BAL fluids from 10 patients with pulmonary sarcoidosis and from five normal volunteers. BAL supernatants from patients with active sarcoidosis showed an enhanced (2- to 8-fold) capacity to induce chemokinesis of both endothelial cells and fibroblasts, as measured by increased area of migration and polarized cell movement. There was a marked heterogeneity in the motility of cells from different organ origins, but enhanced cell movement was observed with both endothelial cells and fibroblasts. In contrast, BAL fluids from normal and sarcoid patients were similar in their effect on muscle cells and urothelial cells, whereas pericytes, which responded to BAL fluids from normal subjects or patients with nongranulomatous pulmonary disease, were inhibited by BAL fluids from patients with pulmonary sarcoidosis. The induction of endothelial cell movement in vitro induced by individual supernatants generally correlated with the capacity of BAL cells from these patients to induce angiogenesis in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis

“…In the diseased state, angiogenesis is fundamental for supporting many aspects of tissue inflammation and remodelling 21,22 . Although the role of neovascularization in the pathogenesis of pulmonary sarcoid has not been investigated extensively, microvascular changes have been reported in the areas of ‘alveolitis’ of sarcoidosis patients, 23 and an increase in angiogenic activity has been found in the BALF of sarcoidosis patients 24 . Furthermore, while levels of the pro‐angiogenic molecule, vascular endothelial growth factor, are lower in sarcoid BALF, 25 other angiogenic factors such as monokine induced by interferon (IFN)‐gamma and IFN‐gamma‐inducible protein 10 (IP‐10/CXCL10) have been identified; 13 our results suggest that sADAM33 may be another angiogenic factor that is present in sarcoid BALF.…”

Enhanced CXCL1 production and angiogenesis in adenosine‐mediated lung disease

“…Biopsies from patients with idiopathic pulmonary fibrosis (IPF) have shown increased lung angiogenic potential (6,7), and vascular remodeling has been demonstrated to be important in bronchiolitis obliterans syndrome (BOS) following lung transplantation (8). In addition, bronchoalveolar lavage cells from patients with pulmonary sarcoidosis have an enhanced capacity to induce angiogenesis as compared to nonaffected individuals (9). Although angiogenesis is a feature of numerous chronic lung disorders, the pathways that regulate angiogenesis in the diseased lung are not completely understood.…”

Angiogenesis in Interstitial Lung Diseases

“…Już w 1986 roku Okabe i Takaku [105] zaobserwowali in vitro, że makrofagi chorych na sarkoidozę produkują czynniki pobudzające proliferację komórek śródbłonka naczyń krwionośnych. W 1989 roku ukazały się doniesienia wskazujące na pobudzanie angiogenezy zarówno przez komórki z płynu z płukania oskrzelowo-pęcherzykowego chorych na sarkoidozę [106], jak i przez nadsącz materiału uzyskanego z BAL [107]. Nowotworzenie naczyń krwionośnych było stwierdzone w przebiegu zmian sarkoidalnych w narządzie wzroku [108,109].…”