Canine neutrophil dysfunction caused by downregulation of β2-integrin expression without mutation

• Published in: Veterinary immunology and immunopathology 2009-01, Vol.130 (3), p.187-196
• Main Authors: Kobayashi, Saori, Sato, Reeko, Abe, Yuya, Inanami, Osamu, Yasui, Hironobu, Omoe, Katsuhiko, Yasuda, Jun, Hankanga, Careen, Oda, Shinichi, Sasaki, Juso
• Format: Article
• Language: English
• Subjects: bacterial infections; beta2-integrin; Canine leukocyte adhesion deficiency; CD11b/CD18; Congenital neutrophil dysfunction; cytochrome b; cytosol; disease incidence; disease resistance; dogs; gene expression; immune response; immune system; immunologic diseases; Integrins; messenger RNA; mutation; NADPH oxidase; neutrophils; oxidoreductases; phagocytes; protein synthesis; reverse transcriptase polymerase chain reaction; transcription (genetics)
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2009.02.008

Canine leukocyte adhesion deficiency (CLAD) in Irish setters is caused by genetic defects of leukocyte integrin CD18 leading to recurrent bacterial infections. We report clinical features and analysis of neutrophil function from two mixed-breed canine littermates (one female and one male dog) similar to CLAD. The symptoms of pyogenic infection were first recognized at 3 months of age and since then the patients suffered from recurrent bacterial infections. These clinical findings were strongly suggestive of genetic phagocyte dysfunction. Neutrophil function tests revealed a marked reduction of serum-opsonized zymosan-mediated superoxide production in the two littermates. Neutrophils of the male dog revealed impaired integrin-mediated adherence and phagocytic activity, whereas ability of serum opsonization was normal. There was also a profound decrease of surface expression of CD11b/CD18 and β2-integrin transcript level, detected by real-time RT-PCR without missense mutations unlike CLAD. Immunoblot analysis indicated that protein expression of cytochrome b 558 component gp91 phox, the cytosolic components p47 phox and p67 phox of NADPH oxidase components increased profoundly in the male. Our study suggests that decreased transcriptional levels of β2-integrin without mutations, lead to downregulation of surface expression, resulting in multiple defects in adhesion-related neutrophil functions and consequently, recurrent bacterial infections from puppyhood.