The Journal of Immunology, 2006, 176: 3856-3857.
Copyright © 2006 by The American Association of Immunologists
Comment on "Cutting Edge: TLR4 Deficiency Confers Susceptibility to Lethal Oxidant Lung Injury"
Hiroshi Kubo and
Kota Ishizawa
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan
We read with interest the article by Zhang et al. published in the October 15, 2005 issue (1). They reported that the absence of TLR4 increases susceptibility to hyperoxia-induced lung injury. They clearly demonstrated that antiapoptotic responses were attenuated in TLR4-deficient mice. However, it is well known that the C3H/HeJ mouse strain, which has a Tlr4 gene mutation, well tolerates hyperoxia exposure and oxidative stress (2, 3, 4, 5). We previously presented that C3H/HeJ mice were resistant to hyperoxia-induced lung injury (6, 7) as described previously (2, 3, 5). In our system, TLR4-deficient mice provided from the same source, Dr. S. Akira (Osaka University, Osaka, Japan), were also resistant to hyperoxia exposure (>95% O2) (6, 7) (Fig. 1). An increase in cell counts in BAL fluid and hyperoxia-induced cytokine up-regulation were also attenuated in C3H/HeJ and TLR4–/– mice. These data suggest that TLR4 is involved in susceptibility, not resistance, to oxidant-induced lung injury. In addition, we are concerned about the survival rate of wild type in Zhang’s article since it was much better than the previous reports (8, 9, 10, 11, 12).
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FIGURE 1. Changes in protein concentration in BAL fluid from the mice exposed to hyperoxia (>95% O2). Hyperoxia increased lung permeability in C57BL/6 mice after 48 and 72 h of the exposure. However, C3H/HeJ mice did not respond to hyperoxia exposure. TLR4–/– mice also did not respond to hyperoxia. *, Significantly greater than 0 h in the same group, p < 0.05.
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Taken together, before we conclude that TLR4 has a protective effect against hyperoxia-induced lung injury, more careful analyses about the role of TLR4 signaling in oxidant stress, including the discrepancy between C3H/HeJ and TLR4-deficient mice, are needed.
References
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