Chronic obstructive pulmonary disease (COPD) in the horse is caused by exposure of
susceptible animals to dust and aeroallergens in poorly saved hay and straw. It is
characterized by recurrent episodes of airway obstruction in association with
neutrophilic pulmonary inflammation. As neutrophils have the capacity to secrete a
wide array of potentially histotoxic products such as reactive oxygen species,
proteases and cationic proteins, these cells have been proposed to be key mediators
of the lung injury observed in COPD. The functional status of neutrophils within
both the circulating granulocyte pool and the airways of horses with COPD remains
largely unexplored. Likewise, little is known of the kinetics of airspace neutrophil
recruitment and clearance during and after an acute episode of COPD or indeed the
subsequent fate of these cells.
I have demonstrated in vitro that isolated peripheral blood neutrophils may be primed
by exposure to inflammatory mediators such as lipopolysaccharide, platelet
activating factor and tumour necrosis factor-a. This results in enhanced respiratory
burst activity upon subsequent exposure to secretagogue stimuli. Indeed, priming
was found to be a necessary step in the induction of functional coupling of receptors
for the bacterial peptide fMLP in equine neutrophils.
I have also demonstrated that purified peripheral blood neutrophils undergo
apoptosis constitutively when aged in vitro and that the rate of apoptosis can be
modulated by exposure to a range of pro-inflammatory mediators. In other models
ofneutrophilic inflammation, cells that have undergone apoptosis have been shown
to be recognized by phagocytes such as inflammatory macrophages, engulfed and
degraded without inciting an inflammatory response.
Acute COPD was induced in susceptible horses by exposure to a 5 h hay/straw
challenge. The kinetics and function of airspace neutrophils harvested by
bronchoalveolar lavage and peripheral blood neutrophils was monitored sequentially
for 14 days after challenge. Hay/straw challenge primed both peripheral blood and
airspace neutrophils for an enhanced secretagogue-induced respiratory burst.
Significant degranulation of neutrophils occurred within the airspaces as evidenced
by a marked increase in neutrophil elastase in bronchoalveolar lavage fluid. As the
pulmonary inflammation resolved, airspace neutrophils underwent apoptosis and
were phagocytosed by alveolar macrophages in vivo. This work demonstrates
significant upregulation of neutrophil function in horses with COPD and provides
evidence of a pivotal role for neutrophil apoptosis in the resolution of the pulmonary
neutrophil burden in this disease.