Emerging Diseases - University of Georgia College of Veterinary ...

HorsesThe Georgia horse industry is experiencing significant growth as more than250,000 horses reside in this state. Equine-related services contribute about$750 million to the state’s economy. These numbers are expected to rise asGeorgia’ population continues to grow. The number of new equine trainingprograms in the Southeast continues to expand, and more professionaltrainers have moved to the Southeast. With this growth comes anincreasing concern about equine colic and laminitis. These diseasescause major losses to the equine industry. Thus, VMES researchershave focused on identifying better ways of treating horses with thesediseases. To date, researchers have determined the effects of bacterial toxinsabsorbed during serious episodes of colic, developed treatments that inhibitaction of some toxins, developed improved techniques to anesthetize horses, andidentified the earliest changes that occur in the digit of horses that develop acutelaminitis. It is the researchers’ goal to learn more about the development of thesediseases so that they can design appropriate measures to prevent them in thefuture.Preventing LPS-monocyte interactions withanti-equine CD14 monoclonal antibodiesEndotoxemia is associated with leadingcauses of death in horses of all ages. Therefore,our long-term goals are to identify themolecular mechanisms responsible for thedeleterious effects of endotoxin and then todevelop appropriately targeted therapeuticinventions. During the past year, we have madesignificant progress to meet these goals. Thisincludes cloning of equine CD14, whichincludes the principal endotoxin receptor.Comparison of the DNA and protein sequencesof this receptor to those of CD14 from otherspecies has revealed two regions that areessential for binding endotoxin and transmittingproinflammatory signals to the interior of thecell. In the future, we plan to bioengineerspecific alterations in the latter region of CD14to generate a recombinant protein that will bindendotoxin strongly but not transmit thedeleterious signals into the cell. Alternatively,the cloned gene may also be used to generaterecombinant equine CD14 protein and thenmonoclonal antibodies directed against thereceptor. Similar anti-CD14 antibodies havebeen shown to prevent endotoxin binding toCD14 in other species and thus effectivelyblock endotoxin’s ill effects. In additionalresearch, we have also identified a new class ofendotoxin antagonists derived from a specifictype of plant bacteria. Our data show that thesenatural antagonists efficiently block endotoxin’saction in horse cells. In summary, we now havethree exciting new ways to interfere with theeffects of endotoxemia in horses and havedeveloped unique tools for studyingthe molecular basis of endotoxin’sactions.James N. Moore, Michel L.Vandenplas, Michelle H. Barton,and Russell W. Carlson*jmoore@calc.vet.uga.edu*Complex Carbohydrate ResearchCenter18Dr. Ray Kaplan conducting field investigations on equinecyathostomes (parasitic worms).Mechanisms of resistance tomacrocyclic lactone drugs inequine cyathostomesParasite drug resistance isrecognized globally as one of thegreatest health threats to grazinghorses, with drug-resistantcyathostomes (small strongyles)