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Lancet. 2002 Oct 12;360(9340):1144-9.
Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study.
Putsep K, Carlsson G, Boman HG, Andersson M.
Karolinska Institutet, Stockholm, Sweden.
BACKGROUND: Antibacterial peptides, such as defensins and LL-37, are natural bactericidal components similar in potency to classic antibiotics. These peptides are produced at mucosal linings in the body and the skin, and by leucocytes such as neutrophils and natural killer cells. Patients with morbus Kostmann-a severe congenital neutropenia-are treated by recombinant granulocyte-colony stimulating factor, which restores their levels of neutrophils. Despite this treatment, patients still have recurrent infections and periodontal disease. Our aim was to investigate if defensins and LL-37 are deficient in patients with morbus Kostmann. METHODS: We studied samples of neutrophils, plasma, and saliva from six patients with congenital neutropenia and 22 healthy controls for presence of antibacterial peptides. Neutrophils were analysed by high-performance liquid chromatography and mass spectrometry for alpha-defensins. All samples were analysed by western blot for cathelin-LL-37 (precursor of LL-37) and LL-37. Neutrophils were also tested for lactoferrin and ability to produce oxidative burst. FINDINGS: Neutrophils from patients with morbus Kostmann were deficient in cathelin-LL-37 and had reduced concentrations of a-defensins HNP1-3. No cathelin-LL-37 could be detected in plasma and saliva from patients. One patient with morbus Kostmann who had had bone-marrow transplantation had almost normal concentrations of LL-37. Lactoferrin concentrations and oxidative burst were normal in all patients. All patients with morbus Kostmann had severe periodontal disease, apart from the individual who had had a bone-marrow transplant, whose dental status was normal. INTERPRETATION: Antibacterial peptides are a vital part of the first line of antibacterial immune defence. Deficiency in saliva LL-37 accords with occurrence of periodontal disease in patients with morbus Kostmann.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12387964&dopt=Abstract
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