Recent Research: Experimental Applications of Pertussis Toxin and Cholera Toxin

The List Labs Citation Database is a robust tool for researchers. It offers thousands of papers showing how List Labs products are used experimentally. Researchers can search for keywords specific to their fields of study and learn how others in that field have used our toxins and antigens.

In this article, we will explore experimental applications for two of our most popular products: Pertussis Toxin (Products #180, #181 and #184) and Cholera Toxin (Product #100B). This article is not exhaustive – we will focus on recent research – but it offers a survey of ways in which List Labs is helping to get science done.

Pertussis Toxin Applications

Experimental autoimmune encephalomyelitis (EAE) is an induced autoinflammatory condition of the central nervous system. It is used in rodents as a model of demyelinating diseases such as multiple sclerosis and of T-cell-mediated autoimmune disease in general. Inducing EAE usually uses isolated myelin proteins or homogenate along with pertussis toxin to open the blood-brain barrier and allow T-cells access to the CNS. Many citations in the database note this use of those products.

But that’s far from the only way researchers have found to use List Labs’ pertussis toxin. An international team of researchers found that pertussis toxin reduces cellular damage following ischemic strokes. Another used it in their study of myocarditis. A Michigan team used pertussis toxin to develop an innovative high-molecular-weight mass spectrometry application. And of course several research groups used it developing assays and treatments for whooping cough.

Cholera Toxin Applications

The applications for cholera toxin are equally diverse. Besides treatments for cholera, researchers recently used the toxin to study the role of bone morphogenetic proteins and mesenchymal stem cells in breast cancer, as well as TRAIL therapy to treat such cancers. Other cancer researchers looked at hemocyanin as a treatment for bladder cancer, using List’s cholera toxin.

Investigators studied vaccines against Helicobacter pylori, which is known to cause peptic ulcers and is a risk factor for gastric cancer.

Food allergies are a serious and growing problem. Our citation database lists studies that used cholera toxin to aid in the study of allergies to several common foods (especially peanuts). Cholera toxin was also studied as an adjuvant for intranasal vaccines and used to investigate the role of immunoglobulin E (IgE) in anaphylactic shock—an extreme and potentially fatal allergic reaction.

Cholera toxin was even used to study the cellular mechanisms of Yersinia pestis, the pathogen that causes bubonic plague.

This is only a brief survey of recent research using two of List Labs’ more popular products. It illustrates both the wide range of applications for List’s bacterial toxins and the utility of the List citation database as a tool to facilitate your literature surveys.

By: Karen Crawford, Ph.D.
President, List Biological Laboratories, Inc.

 

Many bacterial products are potent immune system activators, helping our bodies identify and defend against microbial invasions.  The innate immune system or non-specific immune system is found in animals as well as in plants, fungi and insects and is employed when pathogens break through the outer barrier of skin, scales, or bark.  It is important for any multicellular organism to be able to resist the bacterial pathogens, which can quickly infect tissues that are undefended. Lipopolysaccharides (List products #201 through #434) are frequently used in medical research to challenge the mammalian immune system and induce a cytokine response, setting off a chain of events in the body.  Cytokines are released, attracting macrophages, which attack and “eat” the foreign bodies, and granulocytes, releasing histamines and toxins that are effective in killing bacteria.  Lippolysaccharides have become an important tool in understanding how the body fights infections¹ as well as for understanding inflammation. The chain of signaling set off by lipopolysaccharides includes G-protein activation². LPS has been used to study neurological inflammation^{3, 4}.

Other bacterial “antigens” make potent immune system activators and have slightly more specific effects. For example, challenge with cholera toxin B subunit (List Products #103B – #104) induces lymphoctes to produce a specific kind of T-cell⁵. Activation of the immune system can be quite different, depending on the specific bacteria and virulence factors.  Somehow our bodies have learned to distinguish which bacteria are harmful and which are not; such as in the case of differential activation of immune cells (eosinophils) by probiotic bacteria compared to pathogens such as C. difficile⁶.  Exotoxins from C. difficile are sold as List Products #152 to #155.

 

1. Vassallo M, Mercié P, Cottalorda J, Ticchioni M, and Dellamonica P(2012) The role of lipopolysaccharide as a marker of immune activation in HIV-1 infected patients: a systematic literature review.  Virology J. 9: 174. PMID: 22925532
2. Sangphech N, Osborne BA, Palaga T (2014) Notch signaling regulates the phosphorylation of Akt and survival of lipopolysaccharide-activated macrophages via regulator of G protein signaling 19 (RGS19). Immunobiology 219(9):653-60. PMID:  24775271
3. Kozlowski C and Weimer RM (2012) An Automated Method to Quantify Microglia Morphology and Application to Monitor Activation State Longitudinally In Vivo. PLoS One 7(2): e31814. PMID: 22457705
4. Russo I, Amornphimoltham P, Weigert R, Barlati S, Bosetti F (2011) Cyclooxygenase-1 is involved in the inhibition of hippocampal neurogenesis after lipopolysaccharide-induced neuroinflammation.  Cell Cycle 10(15):2568-73. PMID:  21694498
5. Sun JB, Czerkinsky C, Holmgren J (2012) B lymphocytes treated in vitro with antigen coupled to cholera toxin B subunit induce antigen-specific Foxp3(+) regulatory T cells and protect against experimental autoimmune encephalomyelitis.  J Immunology 188(4):1686-97. PMID: 22250081
6. Hosoki K, Nakamura A, Nagao M, Hiraguchi Y, Tokuda R, Wada H, Nobori T, Fujisawa T (2010) Differential activation of eosinophils by “probiotic” Bifidobacterium bifidum and “pathogenic” Clostridium difficile.  Int Arch Allergy Immunology 152 Suppl 1:83-9. PMID: 20523069