The multifaceted phenomenon of pulmonary ischemia–reperfusion (IR) involves alveolar macrophages, vascular endothelial cells, circulating neutrophils, adhesion factors, free radicals, and a wealth of cytokines. There is a large body of literature describing techniques to attenuate lung IR injury. To date, however, little attention has been focused on the specific mechanisms of lung IR injury itself. The complexity and amplification of the cascades involved in this phenomenon have made investigation of individual components of reperfusion injury difficult to assess.

Characterization of the injury pattern during the early phase of reperfusion is limited. Van Putte and colleagues 1 have attempted to provide insight into and describe some of the key components of this process using a warm blood perfused model. Fiser and coworkers 2 recently described the biphasic nature of reperfusion injury after lung transplantation, beginning with a resident (donor) macrophage response followed by a more intense response of circulating (recipient) neutrophils. Evidence that neutrophils play an important role in lung reperfusion injury has been reported by investigators using leukocyte depletion techniques as well as antibodies directed at adhesion molecules 34. In contrast, some investigators have demonstrated that significant IR injury can occur without neutrophil participation, and in fact neutrophils may have no effect at all in some models of lung injury 5. Our group 6 recently utilized a model that eliminates the role of circulating neutrophils altogether and allowed us to focus strictly on resident macrophages in the lung.

Despite the controversy surrounding the exact role played by circulating neutrophils, they are a critical component of the inflammatory cascade. The study by Van Putte and colleagues 1 clearly demonstrates a specific bimodal, time-dependent course for neutrophil infiltration (30 mins and 3 hours) after reperfusion. This new finding suggests that there is not only a recruitment phase of neutrophils but also a time-dependent activation phase.

The identification of apoptosis within pulmonary IR injury is perhaps one of the more significant findings in the experiment 1. Although this particular study did not investigate the cell signaling mechanisms that are involved in programmed cell death, future studies will certainly better define this mechanism.

Van Putte and coworkers 1 successfully utilized a warm pulmonary IR model to investigate very specific components of a complex physiologic process. Their study verifies some previously described mechanisms of pulmonary IR injury and sheds new light on other mechanisms. Although these findings may not have immediate clinical implications, they certainly add another piece to a complex puzzle.

Abbreviations

Competing interests