TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase
J. Clin. Invest. Jie Fan, et al. 112:1234 doi:10.1172/JCI18696 [Go to this article.]

Figure 6
Effects of sequential challenges of LPS and PGN on MIP-2–induced PMN migration in vivo and transalveolar PMN migration. (a) Data obtained using in vivo air pouch model in which MIP-2 was used to induce migration of PMNs in WT, gp91^phox–/–, and TLR4^–/– mice sequentially challenged with intraperitoneal injections of two doses of LPS or LPS followed by PGN (as described in Methods). Sequential double LPS challenge increased PMN migration to 2.8- and 2.4-fold in WT and gp91^phox–/– mice, respectively, in response to MIP-2, but did not increase PMN migration in TLR4^–/– mice. Sequential injection of PGN 2 hours after LPS, however, markedly increased PMN migration in WT mice, to 4.1-fold that measured in the saline group. In contrast, sequential treatment of LPS and PGN did not significantly increase PMN migration in gp91^phox–/– or TLR4^–/– mice compared with either single LPS or sequential double LPS groups. *P < 0.01 compared with WT animals within the same treatment group; **P < 0.01 compared with WT animals in other treatment groups (n = 3 per group). Numbers (1–7, top) indicate the different groups. (b) To address the role of TLR2 in regulating transalveolar PMN migration in the lung, E. coli was injected intraperitoneally (1 × 10⁵ cells/10 g body wt) into WT and TLR2^–/– mice, and BALF PMNs were counted 4 hours later (n = 3 per group). White bars, saline alone; gray bars, E. coli.