Background and Aims Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor known to dephosphorylate lipopolysaccharide (LPS); however, the role of IAP in the gut response to luminal bacteria remains poorly defined. We investigated immune responses of wild-type (WT) and IAP-knockout (IAP-KO) mice to LPS and Salmonella typhimurium challenges. Methods Cryostat sectioning and standard indirect immunohistochemical staining for major histocompatibility complex (MHC) class II molecules were performed on liver tissue from WT and IAP-KO mice. WT and IAP-KO mice were orally gavaged with S. typhimurium; bacterial translocation to mesenteric nodes, liver, and spleen was determined by tissue homogenization and plating. In other experiments, WT and IAP-KO mice received intraperitoneal injections of LPS, with subsequent quantification of complete blood counts and serum interleukin (IL)-6 by enzyme-linked immunosorbent assay (ELISA). WT and IAP-KO whole blood were plated and stimulated with LPS and Pam-3-Cys, followed by cytokine assays. Results Immunohistologic liver examinations showed increased expression of MHC class II molecules in IAP-KO mice. Following S. typhimurium challenge, WT mice appeared moribund compared with IAP-KO mice, with increased bacterial translocation. WT mice had [50% decrease (P \ .005) in platelets and 1.8-fold (P \ .05) increased serum IL-6 compared with IAP-KO mice in response to LPS injections. IAP-KO whole-blood stimulation with LPS and Pam-3-Cys resulted in increased IL-6 and tumor necrosis factor (TNF)-alpha secretion compared with WT. Conclusions IAP-KO mice exhibit characteristics consistent with local LPS tolerance. Whole-blood response of IAP-KO mice did not reflect systemic tolerance. These data suggest that IAP is a local immunomodulating factor, perhaps regulating LPS–toll-like receptor 4 (TLR4) interaction between commensal microflora and intestinal epithelium.

N6-(Δ2-Isopentenyl)adenosine, a component of tRNA, displays biological activity in both plant and animal systems. As part of a study of the biological behavior of this nucleoside, its degradation in animal tissues has been studied. An enzyme that catalyzes conversion of this nucleoside to inosine has been partially purified from chicken bone marrow. The enzyme preparation also catalyzes conversion of adenosine to inosine at about 40 times the rate of conversion of N6-(Δ2-isopentenyl)adenosine. A series of analogues of this nucleoside has been tested as substrates. The Δ3-isomer, n-pentyl, isopentyl, and furfuryl derivatives are readily cleaved. Hydroxylated derivatives of the Δ2-isopentenyl side chain, however, do not serve as substrates. Adenosine aminohydrolase from calf intestinal mucosa also catalyzes conversion of N6-(Δ2-isopentenyl)adenosine to inosine, although in order to obtain a measurable rate, the concentration of enzyme must be about 1000 times that needed to catalyze conversion of adenosine.