Increased chemoattractant induced neutrophil oxidative burst, accelerated apoptosis, and dysregulated tyrosine phosphorylation associated with lifelong bacterial infections

Sen Rong Yan, Robert Bortolussi, Thomas B. Issekutz, Andrew C. Issekutz

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

8 Citas (Scopus)

Resumen

A boy with lifelong recurrent bacterial infection at cutaneous and mucosal sites was investigated. PMN oxidative burst to phorbol myristate acetate (PMA) and zymosan was normal but was increased 20- to 50-fold upon C5a or formyl-met-leu-phe (fMLP) chemoattractant stimulation, accompanied by accelerated PMN apoptosis. His PMNs showed increased constitutive tyrosine phosphorylation of 21-, 25-, and 44-kDa proteins, and of src-family kinases (p59hck, p58fgr, and p53/56lyn). Phosphorylation was abnormally enhanced following fMLP stimulation. Expression and activity of the major PMN tyrosine phosphatases, i.e., CD45, CD148, and SHP-1 and -2, was normal. However, dephosphorylation of phospho-p58 fgr and phospho-p53/56lyn by lysates of patient's PMNs was enhanced. Thus, another phosphatase may be overactive, perhaps dephosphorylating a regulatory (inhibitory) site on a protein tyrosine kinase, accounting for the abnormal PMN tyrosine phosphorylation and function. With age (now 13 years), T-cell lymphopenia and loss of T-cell responses developed. This appears to be a unique primary immunodeficiency with abnormal PMN oxidative and apoptotic responses to chemoattractants, dysregulated protein tyrosine phosphorylation, serious bacterial infection, and T-lymphocyte attrition.

Idioma originalEnglish
Páginas (desde-hasta)36-47
Número de páginas12
PublicaciónClinical Immunology
Volumen117
N.º1
DOI
EstadoPublished - oct. 2005

Nota bibliográfica

Funding Information:
This work was supported by grant MT-7684 from the Canadian Institutes of Health Research. SRY was the recipient of an IWK Research Associateship.

ASJC Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

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