Experimental murine acid aspiration injury is mediated by neutrophils and the alternative complement pathway

Abstract

Acid aspiration may result in the development of the acute respiratory distress syndrome, an event associated with significant morbidity and mortality. Although once attributed to direct distal airway injury, the pulmonary failure after acid aspiration is more complex and involves an inflammatory injury mediated by complement (C) and polymorphonuclear leukocytes. This study examines the injurious inflammatory cascades that are activated after acid aspiration. The role of neutrophils was defined by immunodepletion before aspiration, which reduced injury by 59%. The injury was not modified in either P- or E-selectin-knockout mice, indicating that these adhesion molecules were not operative. C activation after aspiration was documented with immunochemistry by C3 deposition on injured alveolar pneumocytes. Animals in which C activation was inhibited with soluble C receptor type 1 (sCR1) had a 54% reduction in injury, similar to the level of protection seen in C3-knockout mice (58%). However C4-knockout mice were not protected from injury, indicating that C activation is mediated by the alternative pathway. Finally, an additive effect of neutrophils and C was demonstrated whereby neutropenic animals that were treated with sCR1 showed an 85% reduction in injury. Thus acid aspiration injury is mediated by neutrophils and the alternative C pathway.

Investigation of young children with severe recurrent wheeze: any clinical benefit?

“…Many individuals will have had trials of bronchodilators and inhaled steroids, and repeated blind trials may cause a delay in establishing an important diagnosis, such as upper airway obstruction or an endobronchial foreign body. Furthermore, for patients in whom aspiration is considered likely, bronchoscopy can provide additional information by measuring BAL neutrophils [17] and fat-laden macrophages [18]. It is important to note that the presence of some fat-laden macrophages in the BAL may be completely normal [19] and this is reflected in the present finding of a larger percentage of patients having fat-laden macrophages in BAL than the percentage with an abnormal pH study.…”

Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis

“…Soluble CR1 also prevented the progression of disease in rat arthritis models, such as monarticular arthritis (39), CIA (40), and tumor necrosis factor (TNF)- (41) and anti-CD59-induced arthritis (42). Treatment with sCR1 in mice reduced acid aspiration injury (43), reperfusion/ ischemia injury of skeletal muscle (44), contact sensitivity and delayed-type hypersensitivity (45), and ultraviolet induction of immunosuppression (46).…”

Gastro-oesophageal reflux disease and non-asthma lung disease

“…Proximal GER creates the potential for aspiration, the outcome of which varies with the chronicity of the events and the volume and nature of the aspirate. Acute pneumonitis results from aspiration of a large volume of acidic fluid [29], and animal studies have shown this to be a biphasic process [30,31]: initial chemical injury followed by an inflammatory phase [32][33][34]. Food particles and low pH act synergistically to produce a more severe injury with a different cytokine profile from that generated by acid alone [35,36].…”