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* MediCity Research Laboratory, and
Department of Medical Microbiology, University of Turku;
Department of Bacterial and Inflammatory Diseases, National Public Health Institute; and
Postgraduate School of Turku University for Biomedical Sciences, Turku, Finland
VAP-1, an ecto-enzyme expressed on the surface of endothelial cells, is involved in leukocyte trafficking between the blood and tissues under physiological and pathological conditions. In this study, we used VAP-1-deficient mice to elucidate whether absence of VAP-1 alters the immune system under normal conditions and upon immunization and microbial challenge. We found that VAP-1-deficient mice display age-dependent paucity of lymphocytes, in the Peyer’s patches of the gut. IgA concentration in serum was also found to be lower in VAP-1–/– animals than in wild-type mice. Although there were slightly less CD11a on B and T cells isolated from VAP-1-deficient mice than on those from wild-type mice, there were no differences in the expression of gut-homing-associated adhesion molecules or chemokine receptors. Because anti-VAP-1 therapies are being developed for clinical use to treat inflammation, we determined the effect of VAP-1 deletion on useful immune responses. Oral immunization with OVA showed defective T and B cell responses in VAP-1-deficient mice. Antimicrobial immune responses against Staphylococcus aureus and coxsackie B4 virus were also affected by the absence of VAP-1. Importantly, when the function of VAP-1 was acutely neutralized using small molecule enzyme inhibitors and anti-VAP-1 Abs rather than by gene deletion, no significant impairment in antimicrobial control was detected. In conclusion, VAP-1-deficient mice have mild deviations in the mucosal immune system and therapeutic targeting of VAP-1 does not appear to cause a generalized increase in the risk of infection.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Finnish Academy, Sigrid Juselius Foundation, and Finnish Cultural Foundation.
2 Address correspondence and reprint requests to Dr. Marko Salmi, MediCity Research Laboratory, Tykistökatu 6A, Turku, Finland. E-mail address: marko. salmi{at}utu.fi
3 Abbreviations used in this paper: SSAO, semicarbazide-sensitive amine oxidase; WT, wild type; MLN, mesenteric lymph node; PLN, peripheral lymph nodes; PP, Peyer’s patches; sIg, soluble Ig.
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