The pathology of aerosolized staphylococcal enterotoxin B (SEB) was studied in the nonhuman primate. Six juvenile rhesus monkeys that received multiple lethal inhaled doses of SEB developed diarrhea and vomiting within 24 hr followed by depression, dyspnea, and shock. Three of 6 animals died by 52 hr. The most striking gross lesion in all 6 monkeys was diffuse severe pulmonary edema. Histologically, edema fluid was present within the peribronchiolar, peribronchial, and perivascular interstitium, alveolar septa, and alveoli. The adventitia of pulmonary vessels was infiltrated by lymphocytes, macrophages, and fewer neutrophils. Numerous large lymphocytes with occasional mitotic figures were within pulmonary vessels, often occluding alveolar capillaries. These cells were strongly immunoreactive with monoclonal antibodies against CD3, establishing them as T cells. Ultrastructurally, endothelial cell junctions were intact, and endothelial cells and type I pneumocytes contained numerous pinocytotic vesicles. Alveolar septal interstitial spaces were expanded by edema. The mechanism of these SEB-induced pulmonary lesions was not determined. We hypothesize that cytokine production by activated T cells may have caused vascular permeability changes leading to widespread pulmonary edema and shock.
Alber G., Hammer DK, and Fleischer B. (1990). Relationship between enterotoxic and T lymphocyte-stimulating activity of staphylococcal enterotoxin B. J. Immunol. 144: 4501-4506.
2.
Anderson TD, Hayes TJ, Gately MK, Bontempo JM, Stem LL, and Truitt GA (1989). Toxicity of human recombinant interleukin-2 in the mouse is mediated by interleukin-activated lymphocytes. Separation of efficacy and toxicity by selective lymphocytes subset depletion. Lab. Invest. 59: 598-612.
3.
Beisel WR (1972). Pathophysiology of staphylococcal enterotoxin, type B (SEB) toxemia after intravenous administration to monkeys. Toxicon10: 433-440.
4.
Bergdoll MS (1970). Enterotoxins. In: Microbial Toxins, Vol. III, SJ Ajil, TC Montie, and S Kadis (eds). Academic Press, London, pp. 265-326.
5.
Bergdoll MS (1983). Enterotoxins. In: Staphylococci and Staphylococcal Infections, Vol. II, CSF Easmon and C Adlam (eds). Academic Press, London, pp. 559-597.
6.
Chapell WA (1960). Animal infectivity of aerosols of monkey B virus . Ann. N.Y. Acad. Sci. 85: 931-934.
7.
Choi Y., Kotzin B., Herron L., Callahan J., Marrack P., and Kappler J. (1989). Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. Proc. Natl. Acad. Sci. USA86: 8941-8945.
8.
Cotran RS, Pober JS, Gimbrone MA, Springer TA, Wiebke EA, Gaspari AA, Rosenberg SA, and Lotze MT (1987). Endothelial activation during interleukin 2 immunotherapy. A possible mechanism for the vascular leak syndrome. J. Immunol . 139: 1883-1888.
9.
Cross CE, Parsons GH, Gorin AB, and Last JA (1982). Pulmonary edema: Emphasis on physiologic and toxicologic considerations. In: Mechanisms in Respiratory Toxicology, Vol. I, H Witschi and P Nettesheim (eds). CRC Press, Inc., Boca Raton, FL, pp. 220-238.
10.
Department of Health and Human Services (1985 ). Guide for the Care and Use of Laboratory Animals, revised ed. NIH publication 86-23. Department of Health and Human Services, Washington, DC.
11.
Feingold MJ (1967). Interstitial pulmonary edema: An electron microscopic study of the pathology of staphylococcal enterotoxemia in rhesus monkeys. Lab. Invest. 16: 912-924.
12.
Fishman AP (1980). Pulmonary edema. In: Pulmonary Diseases and Disorders, Vol. I. McGraw-Hill, New York, pp. 733-750.
13.
Fleischer B. (1991). The human T cell response to mitogenic microbial exotoxins. Curr. Top. Microbiol. Immunol . 174: 53-62.
14.
Gascoigne NRJ (1993). Interaction of the T cell receptor with bacterial superantigens. Sem. Immunol. 5: 13-22.
15.
Hodoval LF, Morris EL, Crawley GJ, and Beisel WR (1968). Pathogenesis of lethal shock after intravenous staphylococcal enterotoxin B in monkeys. Appl. Microbiol. 16: 187-192.
16.
Hunt RE, Johnson AJ, Jett J., Tseng J., Komisar J., Wilhelmsen C., Pitt L., and Ruble D. (1993). Host respiratory protection for lethal staphylococcal enterotoxin B. In: Army Science: The New Frontiers, Military and Civilian Applications. D Kamely, K Bannister, and R Sasmor (eds). Borg Biomedical Books, Saratoga, WY, pp. 71-78.
17.
Johnson HM, Russell JK, and Pontzer CH (1991). Staphylococcal enterotoxin microbial superantigens . FASEB J. 5(12): 2706-2712.
18.
Labrecque N. , Thibodeau J., and Sekaly RP (1993). Interactions between staphylococcal superantigens and MHC class II molecules . Sem. Immunol. 5: 23-32.
19.
Marrack P. and Kappler J. (1990). The staphylococcal enterotoxins and their relatives . Science248: 705-711.
20.
Micusan VV and Thibodeau J. (1993). Superantigens of microbial origin. Sem. Immunol. 5: 3-12.
21.
Mourad W., Al-Daccak R., Chatila T., and Geha RS (1993). Staphylococcal superantigens as inducers of signal transduction in MHC class II-positive cells. Sem. Immunol . 5: 47-56.
22.
Ochi A., Yuh K., Migita K., and Kawabe Y. (1992). Effects of staphylococcal toxins on T-cell activity in vivo. Chem. Immunol. 55: 115-136.
23.
Oyejide A., Tseng J., Komisar J., and Hunt RE (1993). Inflammatory cell types and cytokines in monkey lungs following exposure to aerosolized staphylococcal enterotoxin B. Proceedings, 1993 Medical Defense Bioscience Review, Vol. 3, U.S. Army Medical Research and Development Command, Frederick, MD, pp. 1349-1355.
24.
Pettit GW, Yamada T., Wing DA, and Jahrling PB (1978). Enterotoxic shock in rhesus monkeys: The role of selected bloodborne factors. Circulation43: 398-405.
25.
Pober JS and Cotran RS (1990). Cytokines and endothelial cell biology. Physiol. Rev. 70: 427-451.
26.
Richardson JA and Barkley WA (1988). Vertebrate animal biosafety criteria. In: Biosafety in Microbiological and Biomedical Laboratories, HHS Pub. no. 88-8395, U.S. Government Printing Office, Washington, DC, pp. 30-35.
27.
Roessler WG and Kautter DA (1962). Modification of the Henderson apparatus for studying air-borne infections. Evaluations using aerosols of Listeria monocytogenes. J. Infect. Dis. 110: 17-22.
28.
Rosenberg SA , Lotze MT, Yang JC, Aebersold PM, Linehan WM, Seipp CA, and White DE (1989) Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann. Surg. 210: 474-484.
29.
Rosenstein M., Ettinghausen SE, and Rosenberg SA (1986). Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2 . J. Immunol. 137: 1735-1742.
30.
Schlievert PM (1986). Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 are significantly associated with non-menstrual TSS. Lanceti: 1149-1150.
31.
Soto PJ and Roessler WG (1965). Staphylococcal enterotoxemia: Pathologic lesions in rhesus monkeys exposed by aerosol. Technical Manuscript 226, U. S. Government Printing Office, Washington, DC, pp. 1-16.
32.
Spencer H. (1985). Pulmonary edema and its complications and the effects of some toxic gases and substances on the lung. In: Pathology of the Lung, Pergamon Press, New York, pp. 705-731.
33.
Spero L., Johnson-Winegar A., and Schmidt JJ (1988). Enterotoxins of staphylococci. In: Handbook of Natural Toxins, Vol. IV, MC Hardegree and AT Tu (eds). Marcel Dekker, New York, pp. 131-157.
34.
Tseng J., Komisar JL, Chen JY-J, Hunt RE, Johnson AJ, Pitt L., Rivera J., Ruble DL, Trout R., and Vega A. (1993). Immunity and responses of circulating leukocytes and lymphocytes in monkeys to aerosolized staphylococcal enterotoxin B. Infect. Immun. 61: 391-398.
35.
White J., Herman A., Pullen AM, Kubo R., Kappler JW, and Marrack P. (1989). The Vβ-specific superantigen staphylococcal enterotoxin B: Stimulation of mature T cells and clonal deletion in neonatal mice. Cell56: 27-35.
