Skip to main content

Human neutrophil dysfunction with giant granules and defective activation of the respiratory burst.

Publication ,  Journal Article
Newburger, PE; Robinson, JM; Pryzwansky, KB; Rosoff, PM; Greenberger, JS; Tauber, AI
Published in: Blood
June 1983

We describe a patient whose peripheral blood neutrophils and bone marrow precursors (beyond promyelocytes) contained multiple large azurophilic granules. There were also giant granules in eosinophils, basophils, melanocytes, renal tubules, thyroid, and neurones, but not lymphocytes or monocytes. His clinical course included recurrent (ultimately fatal) infections and severe neurologic impairment. Immunofluorescent staining with fluoroscein- and rhodamine-conjugated antisera to primary and secondary granule markers showed virtually all of the granulocyte granules and rare monocyte granules to be fusion products containing both markers. Electron microscopy showed the granules to be large peroxidase-containing lysosomes. Only rare normal primary and secondary granules were present. Superoxide generation in response to opsonized zymosan was 7.3 nmole/min/10(6) cells (control 8.9); but in response to phorbol myristate acetate, only 2.2 (control 9.4). Nitroblue tetrazolium slides showed 3+ dye reduction in response to opsonized zymosan by 90% of granulocytes (control 91%) and to phorbol myristate acetate by 22% (control 99%), with 71% producing only a minimal 1+ response. Cellular contents of myeloperoxidase and beta-glucuronidase were elevated, but the percent release during exocytic degranulation was equivalent to control. Ingestion of complement-opsonized Staphylococcus aureus and zymosan was also normal. Killing of Staphylococcus aureus was 60% at 90-min incubation (control 92%). Granulocyte cyclic adenosine monophosphate (AMP) content was 4 pmole/10(7) cells (control 3.1). In order to determine whether these characteristics derived from the cells' genetic program or their environment, the patient's bone marrow was grown in long-term culture. Granulocytes produced in vitro demonstrated the same morphology, same defect in activation of nitroblue tetrazolium reduction, and same normal cyclic AMP level as those harvested from peripheral blood. These studies describe a new disorder of granulocytes; the structural similarity to, but biochemical differences from, Chediak-Higashi disease indicate the probable heterogeneity of mechanisms for the same morphological abnormality.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

June 1983

Volume

61

Issue

6

Start / End Page

1247 / 1257

Location

United States

Related Subject Headings

  • Peroxidase
  • Periodic Acid-Schiff Reaction
  • Neutrophils
  • Muramidase
  • Male
  • Lactoferrin
  • Infant, Newborn
  • Immunology
  • Humans
  • Hematologic Diseases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Newburger, P. E., Robinson, J. M., Pryzwansky, K. B., Rosoff, P. M., Greenberger, J. S., & Tauber, A. I. (1983). Human neutrophil dysfunction with giant granules and defective activation of the respiratory burst. Blood, 61(6), 1247–1257.
Newburger, P. E., J. M. Robinson, K. B. Pryzwansky, P. M. Rosoff, J. S. Greenberger, and A. I. Tauber. “Human neutrophil dysfunction with giant granules and defective activation of the respiratory burst.Blood 61, no. 6 (June 1983): 1247–57.
Newburger PE, Robinson JM, Pryzwansky KB, Rosoff PM, Greenberger JS, Tauber AI. Human neutrophil dysfunction with giant granules and defective activation of the respiratory burst. Blood. 1983 Jun;61(6):1247–57.
Newburger, P. E., et al. “Human neutrophil dysfunction with giant granules and defective activation of the respiratory burst.Blood, vol. 61, no. 6, June 1983, pp. 1247–57.
Newburger PE, Robinson JM, Pryzwansky KB, Rosoff PM, Greenberger JS, Tauber AI. Human neutrophil dysfunction with giant granules and defective activation of the respiratory burst. Blood. 1983 Jun;61(6):1247–1257.

Published In

Blood

ISSN

0006-4971

Publication Date

June 1983

Volume

61

Issue

6

Start / End Page

1247 / 1257

Location

United States

Related Subject Headings

  • Peroxidase
  • Periodic Acid-Schiff Reaction
  • Neutrophils
  • Muramidase
  • Male
  • Lactoferrin
  • Infant, Newborn
  • Immunology
  • Humans
  • Hematologic Diseases