Fibroproliferation and mast cells in the acute respiratory distress syndrome

Abstract

Background-Mast cells (MCs), which are a major source of cytokines and growth factors, have been implicated in various fibrotic disorders. To clarify the contribution of MCs to fibrogenesis, lung tissue from patients with the acute respiratory distress syndrome (ARDS) was examined during exudative through to fibroproliferative stages. Methods-Lung tissue was obtained from 17 patients with ARDS who had pathological features of the early exudative stage (n = 6) or the later reparative stages (n = 11), from four patients with idiopathic pulmonary fibrosis, and from three patients with normal lung tissue. Immunohistochemical localisation of tryptase (found in all human MCs), chymase (found in a subset of human MCs), -smooth muscle actin (identifies myofibroblasts), and procollagen type I was performed. Results-Normal lung tissue exhibited myofibroblast and procollagen type I immunolocalisation scores each of <5 and MC scores of 1. Increased scores were defined as myofibroblast and procollagen type I scores of >10 and MC scores of >2. Eighty percent of lung tissue samples from the early exudative stage of ARDS exhibited increased numbers of myofibroblasts, 50% had increased numbers of procollagen type I producing cells, while only 17% had increased numbers of MCs compared with control samples. All samples from the later reparative stages of ARDS had increased numbers of myofibroblasts and procollagen type I producing cells. Increased numbers of MCs were seen in 55% of samples from the reparative stages. There was no significant shift in MC phenotype in the ARDS samples. Conclusions-Increased numbers of myofibroblasts and procollagen type I producing cells were frequently found early in the course of ARDS. MC hyperplasia was unusual during this stage, but was often a feature of the later reparative stages. MCs do not appear to initiate fibroproliferation in ARDS. (Thorax 1998;53:823-829)

Immune Response CC Chemokines, CCL5 and CCL2 Are Associated with Pulmonary Sarcoidosis.

“…This suggests that CCL5 involvement in sarcoid granulomatous formation is important for mononuclear phagocyte, lymphocyte as well as mast cell recruitment. There are reports suggesting the involvement of mast cells in pulmonary sarcoidosis [25][26][27] as well as other fibrotic lung disorders [28][29][30]. Collectively, with our study demonstrating that CCL5 is altered in all stages of sarcoidosis it is conceivable that CCL5 via its recruitment effect on mononuclear cells, including mast cells, could be a key chemokine that is involved in the continuum of intense inflammatory injury during early stages to the more chronic inflammatory/fibrosis during late stages of pulmonary sarcoidosis.…”

Activation of the Renin-Angiotensin System in Hyperoxia-Induced Lung Fibrosis in Neonatal Rats

“…0.001 vs. room air group at the same age. in the course of lung injury and influences respiratory mechanics [19] . Hyperoxia-induced pulmonary fibrosis is characterized by fibroblast proliferation and myofibroblast differentiation [20] .…”

Lipopolysaccharide-induced endotoxemia in corn oil-preloaded mice causes an extended course of lung injury and repair and pulmonary fibrosis: A translational mouse model of acute respiratory distress syndrome

“…Human ARDS develops over a ≤7day period; in this time frame, the initial exudative/inflammatory stage is followed by a proliferative tissue repair stage; and after 3 weeks, the repair phase can culminate in pulmonary fibrosis (i.e. in two-thirds of ARDS patients) [7–9]. Although the incidence and mortality of ARDS has declined over recent years [3, 10], the mechanisms that regulate the pathogenesis and resolution of ARDS are incompletely understood, and there are still no effective pharmacological or cell-based treatments for this disease.…”