Abnormal Bactericidal, Metabolic, and Lysosomal Functions of Chediak-Higashi Syndrome Leukocytes

Root, Richard K.; Rosenthal, Alan S.; Balestra, Dominic J.

doi:10.1172/jci106854

Cited by 336 publications

(120 citation statements)

References 35 publications

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“…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].…”

Section: Discussionsupporting

confidence: 62%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Kjeldsen

Calafat

Borregaard

1998

Journal of Leukocyte Biology

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The abnormal giant granules of ChediakHigashi syndrome (CHS) neutrophils in humans are thought to be derived from both azurophil and specific granules, whereas the presence of gelatinase granules and their contribution to giant granule formation has not been investigated previously. We have examined the ultrastructure and mobilization of neutrophil granules from a patient with CHS by immunogold electron microscopy and exocytosis experiments of isolated leukocytes. The giant granules contained the azurophil granule components myeloperoxidase and CD63. We found no evidence of involvement of specific or gelatinase granules in the formation of giant granules because lactoferrin and gelatinase were contained in normalappearing peroxidase-negative granules. On stimulation of leukocytes with N-formyl-methionyl-leucylphenylalanine and the calcium ionophore, ionomycin, there was a diminished exocytosis of myeloperoxidase in CHS compared with a healthy control, indicating a lack of mobilization of the giant granules. On the other hand, there was a normal or augmented release of lactoferrin and gelatinase in CHS neutrophils, with gelatinase granules being the most easily mobilized, as known from normal neutrophils. In conclusion, giant granules from CHS neutrophils originate from azurophil granules but not from the specific and gelatinase granules. J. Leukoc. Biol. 64: 72-77; 1998.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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

Kjeldsen

Calafat

Borregaard

1998

Journal of Leukocyte Biology

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“…1, Tables 2 and 3). This is in contrast to the findings of others who have noted normal phagocytosis but delayed killing of some bacterial strains by granulocytes from CHS patients (Root, Rosenthal and Balestra, 1972) and from beige mice (Gallin et al, 1974). These granulocytes have been shown to have a specific protease deficiency (Vassalli et al, 1978).…”

Section: Discussioncontrasting

confidence: 99%

ABSCESS INDUCTION IN BEIGE (bg/bg) MUTANT MICE

Finlay‐Jones

Shellam

Boyden

et al. 1984

Aust J Exp Biol Med

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Summary Humans with Chediak‐Higashi Syndrome (CHS) and several animal species with similar defects have been reported to have increased susceptibility to infection, including abscess formation, associated with granulocyte abnormalities. Those defects were investigated by comparing mice of the SB/Le strain, homozygous for the beige mutation, with their heterozygous littermates and with normal BALB/c mice with respect to the ability to form intraabdominal abscesses. Mice were autopsied 7 days after the intraperitoneal inoculation of a mixture of Bacteroides fragilis, Escherichia coli and an abscess‐potentiating agent, bran. Although homozygous beige mice formed more numerous abscesses than controls, the total abscess sizes and bacterial contents were not significantly different. Histopathologically, the abscesses resembled those in normal mice. Phagocytic killing assays using granulocytes from beige mice of the SB/Le and C57BL/6J strains showed no significant differences between homozygous beige mice and controls. Within the context of these experiments in which neutrophil function in vivo and in vitro was examined with respect to anaerobic and facultative Gram‐negative bacteria, it is concluded that beige mice can respond adequately to an infectious bacterial challenge. The increased susceptibility to an infection seen in various species with CHS‐like disease may relate to virulence factors of the infecting organisms and defects in host defences documented by others but not manifest in these experiments.

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“…Abnormalities include poor mobilization of neutrophils from the marrow [31], defective chemotactic response of neutrophils and monocytes [32,33] and decreased bactericidal activity [34]. In vivo skin window studies also demonstrated defective neutrophil migration [32].…”

Section: Discussionmentioning

confidence: 99%

Chediak-Higashi Syndrome: Report on Five Saudi Arab Children and Review of the Literature

et al. 1993

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Abnormal Bactericidal, Metabolic, and Lysosomal Functions of Chediak-Higashi Syndrome Leukocytes

Cited by 336 publications

References 35 publications

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

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

ABSCESS INDUCTION IN BEIGE (bg/bg) MUTANT MICE

Chediak-Higashi Syndrome: Report on Five Saudi Arab Children and Review of the Literature

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