Bagley Kenneth C, Abdelwahab Sayed F, Tuskan Robert G, Fouts Timothy R, Lewis George K
Division of Vaccine Research, Institute of Human Virology, University of Maryland Biotechnology Institute, and Department of Microbiology, University of Maryland School of Medicine, Baltimore 21201, USA.
J Leukoc Biol. 2002 Nov;72(5):962-9.
Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella pertussis. PT is a powerful mucosal adjuvant whose cellular target and mechanism of action are unknown; however, emerging evidence suggests that dendritic cells (DC) may be a principal adjuvant target of PT. Here, we investigate the mechanism underlying the effects of these toxins on human monocyte-derived DC (MDDC) in vitro. We found that the effects of PT and AT on MDDC, including maturation, are mediated by cyclic adenosine monophosphate (cAMP). In this regard, adenosine 5'-diphosphate-ribosylation-defective derivatives of PT failed to induce maturation of MDDC, whereas dibutyryl-cAMP (d-cAMP) and Forskolin mimic the maturation of MDDC and dominant inhibition of cytokine production induced by these toxins. Also, cAMP-dependent kinase inhibitors blocked the ability of PT, AT, d-cAMP, and Forskolin to activate MDDC. Taken together, these results show that the effects of PT and AT on MDDC are mediated strictly by cAMP.
百日咳毒素（PT）和腺苷酸环化酶毒素（AT）是百日咳博德特氏菌产生的AB型肠毒素。PT是一种强大的黏膜佐剂，其细胞靶点和作用机制尚不清楚；然而，新出现的证据表明，树突状细胞（DC）可能是PT的主要佐剂靶点。在这里，我们研究了这些毒素在体外对人单核细胞衍生的DC（MDDC）作用的潜在机制。我们发现，PT和AT对MDDC的作用，包括成熟，是由环磷酸腺苷（cAMP）介导的。在这方面，PT的腺苷5'-二磷酸核糖基化缺陷衍生物未能诱导MDDC成熟，而二丁酰-cAMP（d-cAMP）和福斯可林模拟了MDDC的成熟以及这些毒素诱导的细胞因子产生的显性抑制。此外，cAMP依赖性激酶抑制剂阻断了PT、AT、d-cAMP和福斯可林激活MDDC的能力。综上所述，这些结果表明PT和AT对MDDC的作用严格由cAMP介导。
