Proteinase Inhibitory Function in Inflammatory Lung Disease

Abstract

This study examines the bronchial alveolar lavage (BAL) samples from a group of patients with acute bacterial pneumonia (n = 13) and makes a comparison with a control group (n = 5). The proteinase inhibitory capacity was examined and found to be composed primarily of alpha 1-proteinase inhibitor (PI, alpha 1-antitrypsin) and, to a lesser extent, bronchial mucosal inhibitor. Although the average PI concentration was elevated approximately 5-fold in the pneumonia group, its inhibitory function against elastase was decreased 15-fold when compared with that in the control group. The pneumonia group showed an increased concentration of immunologically identified elastin-derived peptides. Some of the BAL fluid from patients with pneumonia showed elastolytic activity against amorphous insoluble lung elastin. The majority of the elastase appears to be of neutrophil origin. Bronchial mucosal inhibitor is shown to be a component of both normal and pneumonia BAL fluids by both immunologic quantitation and by its resistance to perchloric acid inactivation. Compared with those from control subjects, BAL samples from patients with acute bacterial pneumonia showed a decreased proteinase inhibitor function and both increased elastolytic activity and elastin-derived peptide concentration.

Oxidative regulation of neutrophil elastase-alpha-1-proteinase inhibitor interactions.

“…In association with these findings, analyses of the ac-l-PI status in these pathologic samples revealed the presence of uncomplexed, inactive, and proteolyzed antiproteinase (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Because the loss of a-l-PI function represents a pivotal step in the pathogenesis ofelastasemediated damage, increasing attention has focused on the identification of those processes capable of inactivating the antiproteinase.…”

“…The detection of active neutrophil elastase and modified a-I -PI in tissues and fluids recovered from inflammatory sites is thought to represent a critical component in the pathogenesis of tissue damage (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) (5)(6)(7)(20)(21)(22). Oxidized a-1-PI is completely unable to inhibit PPE, but retains considerable inhibitory activity for neutrophil elastase (3,25).…”

“…Although other oxidant sources (i.e., hyperoxia, cigarette smoke, or environmental pollutants; e.g., see References 8,73, and 74) and other proteinases (leukocyte or bacterial; references 17-19 and 75) may also contribute to this scheme, it seems clear that triggered neutrophils alone can directly mediate all of these effects. The ability of the neutrophil to release active elastase in the presence of a-1-PI could be useful in physiologic events such as fibrinolysis, wound healing, or host defense, but under pathological conditions, the indiscriminant release of unregulated elastase could exert powerful and longlasting proinflammatory effects (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Finally, these data lend support to our premise that chlorinated oxidants may play a more general role in controlling proteinase activity (76).…”

“…fluids have been shown to contain free neutrophil elastase activity (for recent examples see References [5][6][7][8][9][10][11][12][13][14][15][16]. In association with these findings, analyses of the ac-l-PI status in these pathologic samples revealed the presence of uncomplexed, inactive, and proteolyzed antiproteinase (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Persistent Elastase/Proteinase Inhibitor Imbalance during Prolonged Ventilation of Infants with Bronchopulmonary Dysplasia: Evidence for the Role of Nosocomial Infections

“…The question of whether such a BAL imbalance persists in BPD infants still requiring MV after 28 d of life has not been addressed. Furthermore, prolonged BPD is often associated with nosocomial lung infections, and the role of such infections in elastolytic damage has been recently emphasized in both acute and chronic lung disease (8,9). We designed a prospective study to answer the following questions: I ) Is severe BPD that still requires mechanical ventilation at d 28 associated with elastase-proteinase inhibitor imbalance?…”