Bovine leukocyte adhesion deficiency: a brief overview of a modern disease and its implications

Bovine Leukocyte Adhesion Deficiency (BLAD) is a genetic disease of cattle affecting the hematopoietic system. In the last decade BLAD has become a disease of economic importance in the dairy industry. As such, this overview describes the chronological developments and thinking that led to the elucidation of BLAD as a distinct disease entity from previous models in canine and human populations. All species affected exhibit symptoms of chronic and recurrent infections. Necrotic and/or gangrenous infections of soft tissues are prevalent, as well as secondary infections with bacteria or fungi. Low birthweight and unthriftiness are key symptoms of neonates in all species affected by LAD. Dermatomycoses and impaired pus formation are also common findings. The physiological basis for BLAD is a deficiency in leukocyte (particularly neutrophil) chemotactic and phagocytic properties. The inhibition of diapedesis in the inflammatory response prevents normal immune reactions to invading pathogens. Chronic infections are a consequence of the faulty immune mechanisms. The biochemical etiology of BLAD involves cell surface glycoprotein molecules known as integrins. These are responsible for cell-cell interactions necessary for neutrophils to adhere to vascular endothelium in a normal individual. Experiments using monoclonal antibodies to block LFA-1, Mac-1, and p150,95 (three integrins vital for cell-cell interactions) mimic BLAD symptomatology and have led to the discovery of the reciprocal Intercellular Adhesion Molecule (ICAM). Through pedigree analysis and biochemical detection with restrictive endonucleases BLAD has been isolated genetically to a single gene locus. The economic significance and prophylaxis are briefly discussed. In addition, the beneficial aspects of the study of BLAD are addressed. There are advantages of producing a BLAD-like state in preventing transplant rejection, ischemia-reperfusion injury, and other scenarios arising from the deleterious effects of the inflammatory response.