Delay of LPS-induced acute lung injury resolution by soluble immune complexes is neutrophil dependent

Abstract

Delay of LPS-induced acute lung injury resolution by soluble immune complexes is neutrophil dependent.Shock 32(3):276-285, 2008. To the Editor: We read with great interest the article by Wu et al. (1) describing the role of immune complexes and neutrophils in a rat model of LPS-induced lung injury. The authors found that inhibition of Fc receptors (FcRs) attenuates lung injury in LPS-treated rats supposedly due to formation of soluble immune complexes after administration of LPS. They also studied expression of FcRs receptors on purified neutrophils from rats and further showed that these receptors regulate neutrophil functions, including apoptosis. In addition, the inhibition of apoptosis of neutrophils was mediated by PI3-K and ERK pathways. We had similarly discovered that mice deficient in FcRs are protected from LPS-induced lung inflammation/injury (2). This was most likely due to inability of immune complexes such as anti-KC[chemokine(CXC motif) ligand 1 (CXCL1)] autoantibody:KC complexes present in these mice to interact with their specific receptors. Moreover, we showed that immune complexes (containing anti-IL-8 autoantibody:IL-8 complexes) purified from lung edema fluids from patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) inhibit apoptosis of human blood neutrophils acting via FcRs (3). In addition, we observed that key components of the FcR signaling pathway, Src, Syk, PI3-K, and ERK, may be involved in regulation of neutrophil apoptosis by the complexes (3). The 2 latter proteins were also shown to control the effect of immune complexes on apoptosis of rat neutrophils by Wu et al. (1). Finally, our laboratory reported that immune complexes present in alveolar spaces of patients with ARDS may facilitate neutrophil adhesion by enhancing the level of the expression of ICAM-1 on endothelial cells in the lung (4). Moreover, Wu et al. (1) pointed out that the composition of immune complexes that appear in LPS-treated rats is not known at present. However, we have presented solid evidence that immune complexes containing autoantibodies against chemokines, IL-8 in humans, and KC in mice may contribute to the inflammatory processes in ALI/ARDS (2-5). Importantly, the levels of anti-IL-8 autoantibody:IL-8 complexes correlated with mortality in patients with well-established ARDS and were predictive of development of ARDS in patients at risk for this disease (5). Finally, the use by Wu et al. (1) of anti-human antibodies to block and study function of FcRs in rats seems controversial taking into consideration the differences in receptor types expressed by human and rat neutrophils (6). In summary, the studies by Wu et al. (1) and our group (2-5) indicate that immune complexes and FcRs may play an important role in the pathogenesis of ALI/ARDS. Anna K. Kurdowska Agnieszka Krupa Rafal Fudala University of Texas Health Science Center Tyler, Texas