Oral administration of bovine lactoferrin upregulates neutrophil functions in a dog with familial β2-integrin-related neutrophil dysfunction

Lactoferrin, a glycoprotein present in neutrophils and exocrine secretions, plays important roles in host defense. Administration of bovine lactoferrin has been reported to modulate various neutrophil functions. We found a mixed-breed male dog with novel familial neutrophil dysfunction. The disorder was caused by a decrease of β2-integrin expression encoding CD18 without mutation. Antibiotics therapy alone did not influence a series of neutrophil functions in the same dog. We examined the effects of oral administration of bovine lactoferrin on the neutrophil function and clinical symptoms in the same dog. Oral chronic administration of bovine lactoferrin increased neutrophilic β2-integrin gene expression comparable to normal dogs, followed by the upregulation of surface CD18 expression. Concurrently, the superoxide production, phagocytic activity and adherence that were β2-integrin-related neutrophil functions increased to normal canine levels. The chronic inflammation from bacterial upper respiratory infections and pneumonia was also alleviated in the dog. Our results indicate that oral treatment with bovine lactoferrin increases neutrophil β2-integrin transcript level, leading to the upregulation of neutrophil functions and improvement of clinical symptoms in the dog with familial neutrophil dysfunction.