Reply

Abstract

Reply: In response to the comments of Kurdowska et al. on our recent online published article (1), few points from our group are addressed in the succeeding sentences. First, we are aware of and appreciate the efforts made by Dr. Kurdowska's group to verify the role of anti-IL-8/IL-8 complex in the pathogenesis of ALI/ARDS in both mice and humans. Second, despite the fact that we would like to believe immune complexes appear in bronchoalveolar fluid (BALF) of LPS-treated Sprague-Dawley rats are anti-macrophage inflammatory protein (MIP) 2/MIP-2 (IL-8 in rats) complexes as suggested by Dr. Kurdowska, the only supporting evidence in our hand so far is LPS treatment significantly increases the levels of MIP-2 in BALF of the treated rats, which obviously is not enough for us to make such claim at present. Besides anti-MIP-2/MIP-2 complexes, anti-albumin/albumin complexes may also be an alternative candidate because the soluble form of these complexes can exacerbate LPS-induced ALI and increase the survival and activities of proinflammatory neutrophils via FcγRs (1). Studies regarding the true identity of the immune complexes increased by LPS in BALF of the treated rats are still under investigation at present. Third, the reason to use anti-human decoy antibodies F(ab)2 to block and study function of FcγRs in rats is because 1) no anti-rat decoy antibodies (blockers of FcγRI, FcγRII, and FcγRIII) are commercially available; 2) we realize that normal anti-human CD16 (FcγRIII), anti-human CD32 (FcγRII), and anti-human CD64 (FcγRI) antibodies can cross react and bind to rat neutrophils isolated from BALF (1); and 3) a strong sequence homology (70%-95%) of the extracellular regions of FcγRs is found between murine and humans (2). Our results clearly demonstrate that decoy antibodies can significantly block the binding of fluorescein isothiocyanate-labeled anti-human FcγR antibodies to rat neutrophils and anti-CD32 (FcγRII) and Anti-CD64 (FcγRI) decoy antibodies can reduce LPS-induced ALI in rats. These results suggest FcγRII and FcγRIII on rat neutrophils may play an important role in the pathogenesis of LPS-induced ALI because human FcγRIIA and rat FcγRIII, human FcγRIIb and rat FcγRIIb, and human FcγR IIIA and rat FcγRIV have been predicated to be orthologs (3). Furthermore, FcγRIV may also be involved in LPS-induced ALI in rat. To avoid the confusion, anti-rat decoy antibodies against FcγRs should be used when available to further confirm the types of FcγRs involved in ALI in rats. Fourth, instead of using gene (such as γ-chain) knockout technique (4), decoy antibody blocking strategy has also been proven to be useful in interfering the binding of immune complex to FcγRs and reducing LPS-induced ALI in rats (1). Clinical use of decoy antibodies should be considered in future treatment of ALI/ARDS in humans. Finally, through different animal models, we are glad to see Kurdowska's and our groups share a common view regarding the role of immune complexes, neutrophils, and FcγRs in the pathogenesis of ALI/ARDS. We appreciate Dr. Anna Kurdowska's comments, particularly regarding the differences in receptor types expressed by human and rat neutrophils. Chi-Mei Hsueh Chieh-Liang Wu National Chung Hsing University Taichung, Taiwan.