Mast cell degranulation is related to asthma severity and varies in different airway wall compartments in asthma

Asthma is characterised by excessive ainvay narrowing, airway inflammation and airwa\ remodelling. Mast cells (MC's) can be considered to be a tissue resident cell capable of playing a role in acute and chronic aspects of asthma via secretion and synthesis of a range of chemical mediators. Mast cells contain or synthesise histamine. which contracts smooth muscle, tryptase and chymase that are potent secretagogues and 1L-4 and IL-5 which are important in allergic inflammation. Thus their distribution and activation in different airway wall compartments may relate to the pathophysiological features of asthma. Transverse sections of large and small airways from controls (CO), mild (nonfatal - NFA) and severe (fatal - FA) asthma, n=8 in each group, were stained with the AAI (MC tryptase) monoclonal antibody. MC's (intact and degranulated) were counted in the lumen (LU), epithelium (EP1), inner airway wall (WAi), smooth muscle (ASM), submucosal mucous glands (SMG) and outer airway wall (WAo) and expressed as cells per mm- of the measured area. Degranulated MC's were expressed as a % of total MC's in the different airway compartments. MC density was 5 fold higher in small airways compared ith large airways and highest on the ASM of all airwa) compartments. MC density as increased (p<0.05) in CO and NFA compared with FA in large airways and in NFA and FA compared with CO in small airways. MC density was highest in ASM and SMG in large airways and in the ASM and WAo in small airways. Degranulation was greater (P<0.05) in FA than in NFA and greater in NFA than CO in large and small airways. Degranulation was highest on ASM and SMG in FA and greater than in NFA and CO. We conclude that MC density varies between large and small airways and between airway compartments. Increased numbers of degranulated MC's on ASM and Gland in FA is likely to play a role in excessive airway narrowine.