TY - JOUR
T1 - Localization of cholera toxin in vivo
AU - Peterson, Johnny W.
AU - Lospalluto, Joseph J.
AU - Finkelstein, Richard A.
N1 - Funding Information:
Received for publication April 5, 1972, and in revised form August 11, 1972. This work was part of a dissertation submitted by the senior author in partial fulfilment of the requirements for the Ph.D. degree in Microbiology from The University of Texas Southwestern Medical School. This work was supported in part by USPHS research grant no. AI-08877 to Dr. Finkelstein under the United States-Japan Cooperative Medical Science Program administered by the National Institute of Allergy and Infectious Diseases and USPHS training grant no. 5 T01 AI-00142. The authors express their appreciation to Dr. P. K. Nakane, Department of Pathology, University of Colorado Medical Center, Denver, Colorado, for allowing Dr. Peterson to study the intricacies of the peroxidaselabeled antibody technique in his laboratory. Please address requests for reprints to Dr. Richard A. Finkelstein, Department of Microbiology, The University of Texas Southwestern Medical School, 5323 Harry Hines Blvd., Dallas, Texas 75235. * Recipient of a Presidential Fellowship from the American Society for Microbiology. Present address, Department of Microbiology, The University of Texas Medical Branch, Galveston, Texas.
PY - 1972/12
Y1 - 1972/12
N2 - Immunohistochemical techniques, done with fluorescein- and horseradish peroxidase-labeled antibodies specifically purified by immunoadsorption, were used to show cholera-toxin antigen in intestinal tissues from adult mice injected intraluminally with highly purified cholera toxin. The toxin (choleragen) and natural toxoid (choleragenoid), but not formalin-inactivated toxoids, were specifically and selectively adsorbed uniformly to the entire mucosal surface of the villi and crypt areas. No penetration of toxin into the epithelium or the lamina propria was observed. Ultrastructural localization studies, using the peroxidase-antibody method, revealed the toxin to be on the membranes of the microvilli. Autoradiography with highly purified, tritium-labeled toxin confirmed these observations. It is suggested that specific adsorption of toxin to the brush-border membrane is the initial step in the pathogenesis of cholera, but that an additional process, stimulated by toxin but not toxoid, is essential. This could be activation of adenyl cyclase. The possibility that amounts of toxin or toxin fragments below the limits of detection by the systems used could penetrate cannot be excluded. Since there is a systemic antitoxin response in cholera, this is likely to occur but may not actually be important in the pathogenesis of the diarrhea of cholera.
AB - Immunohistochemical techniques, done with fluorescein- and horseradish peroxidase-labeled antibodies specifically purified by immunoadsorption, were used to show cholera-toxin antigen in intestinal tissues from adult mice injected intraluminally with highly purified cholera toxin. The toxin (choleragen) and natural toxoid (choleragenoid), but not formalin-inactivated toxoids, were specifically and selectively adsorbed uniformly to the entire mucosal surface of the villi and crypt areas. No penetration of toxin into the epithelium or the lamina propria was observed. Ultrastructural localization studies, using the peroxidase-antibody method, revealed the toxin to be on the membranes of the microvilli. Autoradiography with highly purified, tritium-labeled toxin confirmed these observations. It is suggested that specific adsorption of toxin to the brush-border membrane is the initial step in the pathogenesis of cholera, but that an additional process, stimulated by toxin but not toxoid, is essential. This could be activation of adenyl cyclase. The possibility that amounts of toxin or toxin fragments below the limits of detection by the systems used could penetrate cannot be excluded. Since there is a systemic antitoxin response in cholera, this is likely to occur but may not actually be important in the pathogenesis of the diarrhea of cholera.
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U2 - 10.1093/infdis/126.6.617
DO - 10.1093/infdis/126.6.617
M3 - Article
C2 - 4577423
AN - SCOPUS:0015446806
SN - 0022-1899
VL - 126
SP - 617
EP - 618
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -