Distribution of a Dermonecrotic Crude Toxin Preparation from Pasteurella multocida Serotype D in Rats

Abstract

Summary Following systemic application of dermonecrotic crude toxin (DNT) from a sonic extract of Pasteurella multocida type D into 20 young adult male rats, its distribution and time dependence as well as the toxin induced organ alterations were studied. In all animals, liver, kidney, spleen, lymph nodes, thymus, cross‐sections of the nose, duodenum, gastric wall, lung, and adrenal gland were excised, fixed, dehydrated and embedded in glycol methacrylate. The immunoperoxidase‐avidin‐biotin‐complex‐technique was chosen to detect the toxin in various organs. Toxin was found in decreasing amounts in liver, kidney, spleen, lymph nodes and thymus. In the other organs the essay remained negativ. The DNT was responsible for 3 major histopathological findings: a dystrophic alteration of the parenchymic cells of liver, kidney and adrenal gland; a necrosis of the lymphocytes in thymus, spleen and lymph nodes; an accumulation of neutrophilic granulocytes in the altered tissues, mainly, however, in the cortical and medullary sinus of the lymph nodes. Zusammenfassung Der toxische Kulturüberstand von Pasteurella multocida Typ D und seine Verteilung in der Ratte Nach systemischer Gabe des im Meerschweinchenhauttest Dermatonekrose‐positiv reagierenden Rohtoxins aus Pasteurella multocida Typ D wurden die räumliche und zeitliche Verteilung sowie die durch das Toxin hervorgerufenen Organveränderungen in 20 jungadulten, männlichen Ratten demonstriert. Es folgte die Untersuchung von Leber, Niere, Milz, Lymphknoten, Thymus, Nasenquerschnitten, Duodenum, Magenwand, Lunge, und Nebenniere, welche fixiert, entwässert und in Glycolmethacrylat eingebettet wurden. Die Toxindarstellung erfolgte mittels der Immunperoxidase‐Avidin‐Biotin‐Komplex‐Technik. Hinsichtlich der räumlichen Verteilung konnte das Toxin immun‐histochemisch in abnehmender Menge in Leber, Niere, Milz, Lymphknoten und Thymus nachgewiesen werden. In den übrigen untersuchten Organen verlief der Toxinnachweis negativ. In bezug auf die patho‐histologischen Veränderungen traten folgende Hauptbefunde auf: eine dystrophische Veränderung der Parenchymzellen von Leber, Niere und Nebennierenmark, eine Nekrose der Lymphozyten in Thymus, Milz und Lymphknoten und eine Ansammlung von neutrophilen Granulozyten im Bereich der o. g. Veränderungen, insbesondere aber in den Intermediär‐ und Marksinus der Lymphknoten.

A Protein Toxin from Pasteurella multocida Type D Causes Acute and Chronic Hepatic Toxicity in Rats

“…Lesions in our rats were similar to those in studies where toxin was detected in Kupffer cells and leukocytes using immunoperoxidase, avidin-biotin techniques. 21 Endogenous bacterial endotoxins in the portal venous system of the rat probably contribute to liver damage.15 Lipopolysaccharides and Lipid A, even at low doses, markedly reduce hepatobiliary clearance of leukotrienes. Kupffer cells, like macrophages, engulf endotoxin by endocytosis and subsequently release ar- achidonic acid metabolites, cytokines, procoagulants, fibronectin, lysosomal enzymes, and other factors which are vasoactive, chemoattractant, or toxic.…”

“…' Although not commonly recognized in natural disease, pasteurella toxins (PT) also produce important systemic effects, including damage to liver and kidney.6J1 Experimentally, degeneration of hepatocytes has been reported (but not characterized) in piglets given toxin intraperitoneally (250 pg) 22 and by aerosol (125 pg).6 A PT (which also contained endotoxin), when given intradermally to rats, caused "dystrophic alterations" in liver, kidney, adrenal cortex, and lymphoid tissues. 21 Recently we have shown that PT given subcutaneously causes acute cell swelling and necrosis of hepatocytes in pigs.3 Although not adequately documented, these lesions suggest that toxins may cause alterations of vascular tissue or in systems that control metabolism in liver, skeletal muscle, or kidney. Hepatocytes, through production of acute phase proteins of inflammation, have the capacity to reduce growth, particularly of muscle tissue.…”