Myofibroblast involvement in the allergen-induced late response in mild atopic asthma.

Abstract

We undertook a detailed cellular and ultrastructural examination of bronchial biopsies from seven allergic asthmatic patients and 10 nonasthmatic control subjects (five atopic and five nonatopic) to determine the nature of the inflammation that occurs during allergen-induced late-phase responses (LPRs). The asthmatic subjects had mild asthma (FEV1 = 94 +/- 9% predicted; mean +/- SEM) and required only intermittent use of beta 2-agonists. Airway mucosal biopsy specimens were obtained on a single occasion from the nonasthmatic controls and on two occasions from the asthmatic subjects, at 24 h after diluent challenge and 24 h after challenge with allergen 3 wk later. The mean maximal decrease in FEV1 during the late response after allergen challenge was 30%, and that after administration of diluent was 4%. In coded plastic sections, subepithelial cells were counted with both light and electron microscopy, and the numbers present were expressed per 0.1 mm2 of tissue. Light microscopy revealed statistically significant increases in the total number of inflammatory cells (P < 0.02) and in "activated fibroblasts" after allergen challenge (P < 0.05). Electron microscopy showed significant increases after allergen challenge in the total number of eosinophils (P < 0.05) and cells with the ultrastructural features of myofibroblasts. The latter cells constituted 1.5% of cells after administration of diluent, and this increased to 15.5% after allergen challenge (P < 0.05). Mast cells were significantly more abundant in the atopic nonasthmatic controls than in the asthmatic subjects after allergen challenge. The study demonstrates that the profile of inflammatory cells in asthma at 24 h after allergen challenge is distinct from that in stable asthma and in nonasthmatic controls, and that migratory cells with a contractile phenotype appear in greater numbers in the late response. We propose that subjects who repeatedly develop a late response have increased numbers of migrating, contractile cells that may contribute to formation of the increased bronchial smooth-muscle mass observed in fatal asthma.

Identification of Circulating Fibrocytes as Precursors of Bronchial Myofibroblasts in Asthma

“…At this time point many of the cells expressing both CD34 and procollagen I mRNA also were ␣-SMA-positive cells. They localized to areas of collagen I deposition below the BM, in a zone where myofibroblasts accumulate in chronic asthma (12,13) and where myofibroblastlike cells have been previously observed to appear in asthmatic patients 24 h following allergen inhalation (16). The characteristics of these cells and their location in the bronchial mucosa strongly suggested that they were fibrocyte-like cells that had migrated from the peripheral blood and were differentiating into collagenproducing myofibroblasts at the tissue site.…”

“…Although it has been proposed that myofibroblasts originate from airway resident cells, particularly tissue fibroblasts or myocytes (15)(16)(17)(18)(19)(20), there may be a circulating precursor still unidentified. Previous studies (21,22) have described a population of circulating cells, termed fibrocytes, that express fibroblast products as well as the hemopoietic stem cell Ag CD34, enter sites of tissue injury, and localize to areas of extracellular matrix deposition.…”

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

“…The migratory potential of myofibroblasts has been demonstrated following allergen challenge [83], but where they originate, within a matter of hours following allergen challenge, is unknown. Myofibroblasts have contractile properties and express actin filaments but not myosin, and the lineage relationship among fibroblasts, myofibroblasts and smooth muscle cells is not clear.…”

Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts

“…Chronic in¯ammatory airway diseases such as asthma and pulmonary ®brosis are characterized by an increased deposition of extracellular matrix (ECM), concomitant with proliferation and activation of sub-epithelial ®broblasts (Je ery, 1991;Brewster et al, 1990;Gizycki et al, 1997). Fibroblasts are important sources of cytokines, growth factors and mediators that can in¯uence the behaviour of adjacent cell types and thereby contribute to the initiation and resolution of airway in¯ammation.…”