Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is characterised by the emergence of a GPI-defective clonal hematopoiesis. Its clinical features are hemolytic anemia, cytopenia, and thrombosis. Circulating monocytes and granulocytes are largely GPI-defective in PNH patients. This study aims to investigate the granulocyte functional properties in PNH. We analyzed bacterial-dependent intracellular ingestion and the consequent activation of oxidative burst in GPI-defective granulocytes from four neutropenic PNH patients. Our data show a significant increase in the ability of GPI-defective granulocytes to ingest opsonized bacteria. In addition, an impaired respiratory burst effectiveness in response to two independent bacterial stimuli, the N-formyl-MetLeuPhe (fMLP) synthetic bacterial peptide and E. coli, was revealed. The occurrence of neutropenia and the severe impairment of oxidative burst, occurring in chronic granulomatosis disease, were unable to significantly affect phagocytosis. Thus, additional mechanisms, able to differentially affect ingestion ability and respiratory burst effectiveness, have to be hypothesized. The reduced burst effectiveness of GPI-defective granulocytes was maintained after treatment with phorbol 12-myristate 13-acetate, a pharmacological stimulus able to extensively recruit and to trigger intracellular protein kinase C (PKC). Moreover, blocking of PKC has been observed to severely affect granulocyte respiratory burst with a mild effect on the phagocytosis. These data suggest a role for a modulation of intracellular PKC in the pathogenesis of the impaired granulocyte oxidative burst.
| Original language | English |
|---|---|
| Pages (from-to) | 98-107 |
| Number of pages | 10 |
| Journal | American Journal of Hematology |
| Volume | 82 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2007 |
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Keywords
- Granulocytes
- Oxidative burst
- Paroxysmal nocturnal haemoglobinuria
- Phagocytosis
ASJC Scopus subject areas
- Hematology
Cite this
Glycosyl-phosphatidyl-inositol-defective granulocytes from paroxysmal nocturnal haemoglobinuria patients show increased bacterial ingestion but reduced respiratory burst induction. / Cacciapuoti, Carmela; Terrazano, Giuseppe; Barone, Lucia; Sica, Michela; Becchimanzi, Cristina; Rotoli, Bruno; Ruggiero, Giuseppina; Alfinito, Fiorella.
In: American Journal of Hematology, Vol. 82, No. 2, 02.2007, p. 98-107.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glycosyl-phosphatidyl-inositol-defective granulocytes from paroxysmal nocturnal haemoglobinuria patients show increased bacterial ingestion but reduced respiratory burst induction
AU - Cacciapuoti, Carmela
AU - Terrazano, Giuseppe
AU - Barone, Lucia
AU - Sica, Michela
AU - Becchimanzi, Cristina
AU - Rotoli, Bruno
AU - Ruggiero, Giuseppina
AU - Alfinito, Fiorella
PY - 2007/2
Y1 - 2007/2
N2 - Paroxysmal nocturnal hemoglobinuria (PNH) is characterised by the emergence of a GPI-defective clonal hematopoiesis. Its clinical features are hemolytic anemia, cytopenia, and thrombosis. Circulating monocytes and granulocytes are largely GPI-defective in PNH patients. This study aims to investigate the granulocyte functional properties in PNH. We analyzed bacterial-dependent intracellular ingestion and the consequent activation of oxidative burst in GPI-defective granulocytes from four neutropenic PNH patients. Our data show a significant increase in the ability of GPI-defective granulocytes to ingest opsonized bacteria. In addition, an impaired respiratory burst effectiveness in response to two independent bacterial stimuli, the N-formyl-MetLeuPhe (fMLP) synthetic bacterial peptide and E. coli, was revealed. The occurrence of neutropenia and the severe impairment of oxidative burst, occurring in chronic granulomatosis disease, were unable to significantly affect phagocytosis. Thus, additional mechanisms, able to differentially affect ingestion ability and respiratory burst effectiveness, have to be hypothesized. The reduced burst effectiveness of GPI-defective granulocytes was maintained after treatment with phorbol 12-myristate 13-acetate, a pharmacological stimulus able to extensively recruit and to trigger intracellular protein kinase C (PKC). Moreover, blocking of PKC has been observed to severely affect granulocyte respiratory burst with a mild effect on the phagocytosis. These data suggest a role for a modulation of intracellular PKC in the pathogenesis of the impaired granulocyte oxidative burst.
AB - Paroxysmal nocturnal hemoglobinuria (PNH) is characterised by the emergence of a GPI-defective clonal hematopoiesis. Its clinical features are hemolytic anemia, cytopenia, and thrombosis. Circulating monocytes and granulocytes are largely GPI-defective in PNH patients. This study aims to investigate the granulocyte functional properties in PNH. We analyzed bacterial-dependent intracellular ingestion and the consequent activation of oxidative burst in GPI-defective granulocytes from four neutropenic PNH patients. Our data show a significant increase in the ability of GPI-defective granulocytes to ingest opsonized bacteria. In addition, an impaired respiratory burst effectiveness in response to two independent bacterial stimuli, the N-formyl-MetLeuPhe (fMLP) synthetic bacterial peptide and E. coli, was revealed. The occurrence of neutropenia and the severe impairment of oxidative burst, occurring in chronic granulomatosis disease, were unable to significantly affect phagocytosis. Thus, additional mechanisms, able to differentially affect ingestion ability and respiratory burst effectiveness, have to be hypothesized. The reduced burst effectiveness of GPI-defective granulocytes was maintained after treatment with phorbol 12-myristate 13-acetate, a pharmacological stimulus able to extensively recruit and to trigger intracellular protein kinase C (PKC). Moreover, blocking of PKC has been observed to severely affect granulocyte respiratory burst with a mild effect on the phagocytosis. These data suggest a role for a modulation of intracellular PKC in the pathogenesis of the impaired granulocyte oxidative burst.
KW - Granulocytes
KW - Oxidative burst
KW - Paroxysmal nocturnal haemoglobinuria
KW - Phagocytosis
UR - http://www.scopus.com/inward/record.url?scp=33846554212&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846554212&partnerID=8YFLogxK
U2 - 10.1002/ajh.20779
DO - 10.1002/ajh.20779
M3 - Article
VL - 82
SP - 98
EP - 107
JO - American Journal of Hematology
JF - American Journal of Hematology
SN - 0361-8609
IS - 2
ER -