Mast cells in bronchiectasis.
Bronchiectasis (BE) is a chronic severe inflammatory lung disease characterized by frequent bacterial infections and polymorphonuclear neutrophil-dominated inflammatory reaction. We have attempted to elucidate the role of mast cells (MCs) in BE lung inflammation by measuring in the bronchoalveolar lavage fluid (BALF) the MC-derived tryptase levels by radioimmunoassay and immunoblotting and also by measuring the tryptase-like activities in 36 BE patients and in 14 healthy controls. The amount of MC in the lung tissue was assessed by immunohistochemical staining of resected lung tissue samples. Based on the clinical and radiological parameters the patients were divided into subgroups according to the severity of the disease. The MC tryptase concentrations (microg/L; median (range)) in BALF of BE patients were higher compared to healthy controls (4.7(1.4-20.1) and 2.0 (0.1-3.5), respectively, P < 0.01). Tryptase concentrations in the groups of mild, moderate and severe BE were 3.8 (0.9-10.8), 4.3 (3.0-12.6) and 9.6 (1.2-20.1), respectively. All the values differed significantly from those observed in the healthy controls. The tryptase-like activities (nmol/sec/L) in BE patients were also markedly increased (174 (31-2874)) compared to healthy controls (28 (9-45) P < 0.0001). The tryptase-like activities in the patient subgroups were 45 (36-598) in mild, 91 (31-1437) in moderate and 1336 (37-2874) in severe BE. Again, all values differed significantly from those observed in the healthy controls. Moreover, immunoblot experiments disclosed the most intensive immunoreactivity of the 27.5 kD tryptase monomer in BALF of patients with severe BE followed by weaker immunoreactivity in groups of moderate and mild BE and in healthy controls. No significant difference could be observed in the amount of tryptase-positive cells between BE patients and controls. However, the presence of degranulated MCs was more evident in BE lung tissue. Significant correlation could also be observed between the degree of activation of latent procollagenase and tryptase concentration (r = 0.8, P = 0.0004) in BALF of individual BE patients. The observed strong correlation between tryptase levels and disease severity suggests that MCs may be involved in the inflammatory reaction in the BE lung. Importantly, the high levels of tryptase, observed also in patients with mild BE, suggests that activation of and proteinase release from MCs may be one of the reasons for the perpetuation of tissue injury even during the clinically quiescent periods in BE.
Institute of Biomedicine, Department of Anatomy, University of Helsinki. Ruth.Sepper@helsinki.fi
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Sepper
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Konttinen
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Kemppinen
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Sorsa
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Eklund
D000328:Adult; D015153:Blotting, Western; D001987:Bronchiectasis / Q000175:diagnosis* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D053818:Chymases; D017364:Collagenases / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D012697:Serine Endopeptidases / Q000032:analysis; D053802:Tryptases
D018836:Inflammation Mediators; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D017364:Collagenases