Distribution and degranulation of airway mast cells in normal and asthmatic subjects

Abstract

It was hypothesized that the distribution and activation of mast cells across the airway wall may reflect their function in asthma.The density of mast cells (intact and degranulated) within airway compartments in cartilaginous and membranous airways, obtained from autopsies on patients with fatal asthma, nonfatal asthma, and nonasthmatic control cases have been examined.In cartilaginous airways, the mean¡SE density of mast cells in control cases was 27¡9 cells?mm -2 . It was similar in nonfatal asthma (24¡2 cells?mm -2 ) but reduced (pv0.05) in fatal asthma cases (16 ¡ 2 cells?mm -2 ). In membranous airways, the density of mast cells in control cases was 155 ¡ 21 cells?mm -2 and was higher (pv0.05) in cases of nonfatal (270 ¡ 51 cells?mm -2 ) and fatal asthma (219 ¡ 26 cells?mm -2 ). Mast-cell density was greatest on the smooth muscle and mucous glands in cartilaginous airways and on the smooth muscle and outer airway wall in membranous airways. The percentage of degranulated mast cells was higher (pv0.05) in cases of asthma, related to disease severity, and was higher in cartilaginous than membranous airways. Degranulation was greatest on the smooth muscle in fatal asthma cases.Mast-cell distribution and degranulation varies between cartilaginous and membranous airways and across the airway wall. Degranulation of mast cells is related to asthma severity. The increased degranulation in proximal airways may reflect stimulation via the inhaled route.

Do bronchial biopsies represent mast cell density in airways? A stereological study

“…Only mast cells were used for comparing these methods. Mast cells were chosen for initial study for four reasons: 1) they are potent and constitutive inflammatory cells long associated with asthma and now the subject of renewed interest [47][48][49]; 2) they have been shown to stain clearly with the marker for mast cell tryptase employed in the formalin fixed tissues used in the current authors' laboratory; 3) their counts have been found to be highly reproducible; and 4) in proximal airways, they are distributed relatively widely across the airway wall, including the smooth muscle layer and mucous glands [23,44], although their absolute density and level of activation may vary in different compartments and disease states [23].…”

“…Even when using all available biopsies, the resulting case mean generally reflected only 30-40% of the variance in mean mast cell density over the WAt on transverse sections. In part, this would have been due to greater heterogeneity in the distribution of mast cells over the WAt in proximal airways when compared with the WAi [23], as a result of differences between these compartments in the presence or distribution of structural elements, such as smooth muscle, cartilage plates, submucosal mucous glands and blood vessels.…”

“…Since most biopsy studies reporting the density of inflammatory cells have been in mild cases of asthma [3,4,[6][7][8][9][10][11][12][13][14][15][16]22], comparisons with post mortem studies are effectively limited to the small number of such studies that have compared transverse sections from cases of less severe, nonfatal asthma and controls [23,24]. Results of biopsy studies in mild asthma have not been entirely consistent with either results of the post mortem studies using cases of nonfatal asthma, or with each other.…”

“…Mast cells are widely distributed across the WAi, including the smooth muscle layer [23]. Although some authors have implicitly endorsed cell counts in biopsies to a depth of 100-125 mm below the basement membrane, mostly for a variety of other inflammatory cells [40][41][42], a potential problem with using a narrow band of tissue of fixed absolute width when enumerating mast cells is that it will represent a variable fraction of the width of the WAi at the biopsy site, generally a smaller fraction for larger airways.…”

Assessing and accessing the small airways; implications for asthma management

“…In a study by Carroll et al [19], the increased expression of mast cell chymase in the outer area of the distal airways was significantly associated with impaired lung function in individuals with severe asthma. In subjects with severe asthma compared with those with mild to moderate asthma, an increased production of alveolar nitric oxide (NO), but not bronchial NO, was also found [20], implying that a more intense degree of inflammation occurs in the periphery of the bronchial tree in the most severe forms of asthma.…”