Delayed phagocytosis and bacterial killing in Chediak-Higashi syndrome neutrophils detected by a fluorochrome assay: ultrastructural aspects

Abstract

The few studies already published about phagocyte functions in Chediak-Higashi syndrome (CHS) has stated that neutrophils present slow rate of bacterial killing but normally ingest microorganisms. In the present study, both phagocytosis and killing of Staphylococcus aureus were verified to be delayed in neutrophils from two patients with CHS when these functions were simultaneously evaluated by a fluorochrome phagocytosis assay. Electron microscopic examination showed morphologic differences among neutrophils from CHS patients and normal neutrophils regarding the cytoplasmic structures and the aspects of the phagolysosomes. It was noteworthy the presence of giant phagolysosomes enclosing bacteria in active proliferation commonly observed in CHS neutrophils after 45 min of phagocytosis, which corresponded with the impaired bactericidal activity of these leukocytes. The present results suggest that phagocytosis may also be defective in CHS, and point out to the sensitivity of the fluorochrome phagocytosis assay and its application in clinical laboratories.

Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules

“…Stimulation of isolated leukocytes clearly indicated a deficient mobilization of myeloperoxidase and lysozyme on Ionomycin stimulation, indicating an almost complete lack of giant granule mobilization, which may well explain the delayed bacterial killing observed in CHS [7,8]. We found a more pronounced reduction in mobilization of myeloperoxidase than previously published by others [10,11].…”

“…The hallmark of the disease is the presence of giant granules in most nucleated cells, including neutrophils. The propensity for infections in CHS is believed in part to be due to neutropenia and to deficient chemotaxis and delayed bacterial killing of neutrophils [6][7][8]. The latter is most likely caused by reduced content of certain microbicidal/cytotoxic proteins in CHS neutrophils [9] and by diminished mobilization of the giant granules [7,10,11], which contain the majority of the microbicidal substances of neutrophils.…”

Chédiak-Higashi-Steinbrinck syndrome (CHS) in a 27-year-old woman - effects of G-CSF treatment

“…Bellinati-Pires et al [12] saw reduced phagocytosis after 5 min incubation time in one However, in two other investigations by Wolff et al [13] and Root et al [14] leukocyte phagocytosis was normal. In our oxidative burst assay at least the responsiveness to the chemotactic peptide fMLP was strongly enhanced after G-CSF (Table 3).…”

Chédiak-Higashi syndrome: presentation of seven cases

“…[7][8][9] The immunological abnormalities described in CHS are not restricted to phagocyte dysfunction such as reduction of bactericidal capacity and impaired chemotactic activity of phagocytic cells. 10 Other immunologic functions are also affected such as the activity of natural killer cells and antibody-dependent cellmediated cytotoxicity (ADCC). 2,4 According to the recent classification of immunodeficiencies published by the World Health Organization (WHO,1995), CHS is considered to be an inherited metabolic defect.…”