| First Author | Diehl SA | Year | 2014 |
| Journal | Infect Immun | Volume | 82 |
| Issue | 2 | Pages | 773-82 |
| PubMed ID | 24478091 | Mgi Jnum | J:209809 |
| Mgi Id | MGI:5568780 | Doi | 10.1128/IAI.00971-13 |
| Citation | Diehl SA, et al. (2014) G proteins Galphai1/3 are critical targets for Bordetella pertussis toxin-induced vasoactive amine sensitization. Infect Immun 82(2):773-82 |
| abstractText | Pertussis toxin (PTX) is an AB5-type exotoxin produced by the bacterium Bordetella pertussis, the causative agent of whooping cough. In vivo intoxication with PTX elicits a variety of immunologic and inflammatory responses, including vasoactive amine sensitization (VAAS) to histamine (HA), serotonin (5-HT), and bradykinin (BDK). Previously, by using a forward genetic approach, we identified the HA H1 receptor (Hrh1/H1R) as the gene in mice that controls differential susceptibility to B. pertussis PTX-induced HA sensitization (Bphs). Here we show, by using inbred strains of mice, F1 hybrids, and segregating populations, that, unlike Bphs, PTX-induced 5-HT sensitivity (Bpss) and BDK sensitivity (Bpbs) are recessive traits and are separately controlled by multiple loci unlinked to 5-HT and BDK receptors, respectively. Furthermore, we found that PTX sensitizes mice to HA independently of Toll-like receptor 4, a purported receptor for PTX, and that the VAAS properties of PTX are not dependent upon endothelial caveolae or endothelial nitric oxide synthase. Finally, by using mice deficient in individual Galphai/o G-protein subunits, we demonstrate that Galphai1 and Galphai3 are the critical in vivo targets of ADP-ribosylation underlying VAAS elicited by PTX exposure. |
