Pathogenesis of the systemic inflammatory syndrome and acute lung injury: role of iron mobilization and decompartmentalization

Abstract

Changes in iron homeostatic responses routinely accompany infectious or proinflammatory insults. The systemic inflammatory response syndrome (SIRS) and the development of acute lung injury (ALI) feature pronounced systemic and lung-specific alterations in iron/heme mobilization and decompartmentalization; such responses may be of pathological significance for both the onset and progression of acute inflammation. The potential for excessive iron-catalyzed oxidative stress, altered proinflammatory redox signaling, and provision of iron as a microbial growth factor represent obvious adverse aspects of altered in vivo iron handling. The release of hemoglobin during hemolytic disease or surgical procedures such as those utilizing cardiopulmonary bypass procedures further impacts on iron mobilization, turnover, and storage with associated implications. Genetic predisposition may ultimately determine the extent to which SIRS and related syndromes develop in response to such changes. The design of specific therapeutic interventions based on endogenous stratagems to limit adverse aspects of altered iron handling may prove of therapeutic benefit for the treatment of SIRS and ALI.

Recent advances in genetic predisposition to clinical acute lung injury

“…Recently, the role of altered iron mobilization and decompartmentalization in ALI was also reported (51). With this backdrop, it is reasonable that many of the candidate genes studied to date fall within these specific pathways.…”

“…Sadly, this has not been the case for some of the devastating lung diseases, including ALI and ARDS. Consider that, based on an updated review of the literature on genetic associations with lung injury, only 31 genetic association studies have been published, and of those, associations between polymorphisms in only 21 genes and ALI/ARDS phenotypes have been confirmed (11,30,37,51,73,81), as summarized in Table 1.…”

Iron-induced remodeling in cultured rat pulmonary artery endothelial cells

“…Iron has been shown to be a component of the pathogenesis and/or maintenance of acute lung injury (ALI) in experimental animals and human subjects (Lagan et al 2008). The majority of these studies have focused on disturbances in iron homeostasis in the airways resulting from exposure to noxious gases and particles (Turi et al 2004).…”

Miniaturized Extracorporeal Circulation

“…The activated neutrophils can contribute to myocardial damage by infiltrating the myocardium and worsening the mechanism of ischemiareperfusion damage that initiates after aortic cross clamp removal (Paparella et al 2002). Moreover the neutrophils can infiltrate not only the myocardium but also the lungs and the brain (Lagan et al 2008). Usually the neutrophils blood count and the total white blood cell count increase during ECC and over the first 48 hours after the operation (Fromes et al 2002) …”