Impaired natural killer cell recycling in childhood chronic neutropenia with morphological abnormalities and defective chemotaxis of neutrophils
| Autor: | Atsushi Komiyama, Sachihiro Yamada, Yukiaki Miyagawa, Yoshio Uehara, Taro Akabane, Hiroshi Kawai, Kohki Aoyama, Saitoh H, Munehiro Yamazaki |
|---|---|
| Rok vydání: | 1985 |
| Předmět: |
Cytotoxicity
Immunologic Male Interleukin 2 Neutropenia Adolescent Neutrophils Lymphocyte Immunology Biology Biochemistry Natural killer cell Interleukin 21 Interferon medicine Humans Child Lymphokine-activated killer cell Chemotaxis Cell Biology Hematology Immunity Innate Killer Cells Natural Chemotaxis Leukocyte medicine.anatomical_structure Child Preschool Chronic Disease Interferon Type I Interleukin 12 Interleukin-2 Female Agranulocytosis medicine.drug |
| Zdroj: | Blood. 66:99-105 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v66.1.99.99 |
| Popis: | Natural killer (NK) cell activity was measured by a 51Cr-release assay using K562 target cells in 12 neutropenic children. NK cell activity was depressed in four patients who had childhood chronic neutropenia with abnormal neutrophil morphology and chemotaxis. The percentage of lysis at a 40:1 effector-target ratio was 28.4% to 42.1% (P less than .001) of the normal lymphocyte value during the study period (32 to 40 months). NK cell activity was normal in the other eight children with chronic neutropenia without any of these neutrophil abnormalities: lazy leukocyte syndrome, Shwachman syndrome, or dysgammaglobulinemia type I with neutrophil defects. NK cell activity of the four patients was depressed at 5:1 to 40:1 effector-target ratios. The NK cells responded to in vitro interferon (IFN)-alpha and interleukin 2, as did normal lymphocytes, but the activated levels were still lower than those of normal lymphocytes (P less than .01). Because NK cells kill a target through recognition, binding, killing, and detaching, and they repeat this lytic sequence (ie, recycling), the localization of the NK cell defect was further analyzed in the four patients using both 51Cr- release and single cell-in-agarose assays. The patients' NK cells were normal in recognizing, binding, and killing a target but were defective in recycling; the estimated maximum recycling capacity (MRC) values in a four-hour assay were 1.8 to 2.4 (P less than .01), as compared with the normal lymphocyte value of 5.5 +/- 0.6 (mean +/- SD). The stimulation of the effector cells with 1,000 U/mL IFN-alpha did not significantly increase the estimated MRC. These results demonstrate that NK cells are defective in recycling in some type of childhood chronic neutropenia with abnormal neutrophil morphology and chemotaxis. The NK cell deficiency is of clinical interest in terms of its relationship to the recurrent infections, development of malignancy, and dysgranulopoiesis in the disorder. |
| Databáze: | OpenAIRE |
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