title: Canine neutrophil dysfunction caused by downregulation of beta2-integrin expression without mutation.
abstract: 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 beta2-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 beta2-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.
authors.affiliation: Department of Veterinary Medicine, Iwate University, 3-18-8 Ueda, Morioka 020-8550, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Reeko
authors.initials: R
authors.lastname: Sato
authors.forename: Yuya
authors.initials: Y
authors.lastname: Abe
authors.forename: Osamu
authors.initials: O
authors.lastname: Inanami
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yasui
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Omoe
authors.forename: Jun
authors.initials: J
authors.lastname: Yasuda
authors.forename: Careen
authors.initials: C
authors.lastname: Hankanga
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oda
authors.forename: Juso
authors.initials: J
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary; D001483:Base Sequence; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D018821:CD18 Antigens / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics* / Q000276:immunology*; D004285:Dogs; D015536:Down-Regulation; D005260:Female; D066298:In Vitro Techniques; D007781:Lactoferrin / Q000235:genetics; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D008297:Male; D009154:Mutation; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D017931:DNA Primers; D012333:RNA, Messenger; D019255:NADPH Oxidases; D007781:Lactoferrin