Contribution of 92 kDa gelatinase type IV collagenase in bronchial inflammation during status asthmaticus

In order to assess inflammatory features related to severe asthma as compar ed with mild asthma, we investigated the secretion of 92 kDa gelatinase mat rix metalloproteinase (MMP-9) in bronchial lavages of six patients undergoi ng mechanical ventilation (MV) for status asthmaticus (SA) and in six patie nts with mild asthma. Ten healthy nonventilated patients and four patients under MV without preexisting respiratory disease were also investigated. Pa tients with SA were characterized by prominent neutrophilic inflammation (8 2 +/- 4% versus 10% in mild asthma). On the basis of enzymatic and immunolo gical analysis, results showed an acute 10- to 160-fold increase of 92 kDa gelatinase (MMP-9) concentration in epithelial lining fluid (ELF) from pati ents with SA together with activated forms (46 and 26 kDa) of stromelysin-1 matrix metalloproteinase (MMP-3) and detectable concentration of free meta llogelatinolytic activity (1-5 mu g gelatin hydrolyzed/48 h/ml ELF). Concom itant elevated level of tissue inhibitor of metalloproleinase-1 (TIMP-1) wa s shown only in patients with SA, thus counterbalancing, at least partially , excess of activated 92 kDa gelatinase. Acutely enhanced albumin levels we re only observed in patients with SA; Tn addition, 92 kDa gelatinase and al bumin levels were significantly and positively correlated (r = 0.96, p < 0. 0007), suggesting that 92 kDa gelatinase may account for increased bronchia l permeability in patients with SA. Several arguments support: that 92 kDa gelatinase during SA originates both from numerous activated chemoattracted neutrophils and from activated bronchial epithelial cells in response to i n situ lung injury. The fact that no relevant change In ELF, albumin, MMP-9 , MMP-3, TIMP-1, or laminin degradation products was observed during mild a sthma, strongly supports that the mechanism of airway inflammation in SA is quite distinct from that observed in mild asthma.