Abstract
Recent data indicate that integrin-generated signals can modulate different receptor-stimulated cell functions in both a positive (costimulation) and a negative (inhibition) fashion. Here we investigated the ability of β1 integrins, namely α4β1 and α5β1 fibronectin receptors, to modulate CD16-triggered phospholipase activation in human NK cells, β1 integrin simultaneous crosslinking selectively inhibited CD16- induced phospholipase D (PLD) activation, without affecting either phosphatidylinositol-phospholipase C or cytosolic phospholipase A2 (PLA2) enzymatic activity. CD16-induced secretory PLA2 (sPLA2) protein release as well as its enzymatic activity in both cell-associated and soluble forms were also found to be inhibited upon β1 integrin coengagement. The similar effects exerted by specific PLD pharmacological inhibitors (2,3- diphosphoglycerate, ethanol) suggest that in our experimental system, sPLA2 secretion and activation are under the control of a PLD-dependent pathway. By using pharmacological inhibitors (2,3-diphosphoglycerate, wortmannin, ethanol) we also demonstrated that PLD activation is an important step in the CD16-triggered signaling cascade that leads to NK cytotoxic granule exocytosis. Consistent with these findings, fibronectin receptor engagement, by either mAbs or natural ligands, resulted in a selective inhibition of CD16-triggered, but not of PMA/ionomycin-induced, degranulation that was reversed by the exogenous addition of purified PLD from Streptomyces chromofuscus.
| Original language | English |
|---|---|
| Pages (from-to) | 2064-2072 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 162 |
| Issue number | 4 |
| Publication status | Published - Feb 15 1999 |
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ASJC Scopus subject areas
- Immunology
Cite this
β1 integrin cross-linking inhibits CD16-induced phospholipase D and secretory phospholipase A2 activity and granule exocytosis in human NK cells : Role of phospholipase D in CD16-triggered degranulation. / Milella, Michele; Gismondi, Angela; Roncaioli, Paola; Palmieri, Gabriella; Morrone, Stefania; Piccoli, Mario; Frati, Luigi; Cifone, Maria Grazia; Santoni, Angela.
In: Journal of Immunology, Vol. 162, No. 4, 15.02.1999, p. 2064-2072.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - β1 integrin cross-linking inhibits CD16-induced phospholipase D and secretory phospholipase A2 activity and granule exocytosis in human NK cells
T2 - Role of phospholipase D in CD16-triggered degranulation
AU - Milella, Michele
AU - Gismondi, Angela
AU - Roncaioli, Paola
AU - Palmieri, Gabriella
AU - Morrone, Stefania
AU - Piccoli, Mario
AU - Frati, Luigi
AU - Cifone, Maria Grazia
AU - Santoni, Angela
PY - 1999/2/15
Y1 - 1999/2/15
N2 - Recent data indicate that integrin-generated signals can modulate different receptor-stimulated cell functions in both a positive (costimulation) and a negative (inhibition) fashion. Here we investigated the ability of β1 integrins, namely α4β1 and α5β1 fibronectin receptors, to modulate CD16-triggered phospholipase activation in human NK cells, β1 integrin simultaneous crosslinking selectively inhibited CD16- induced phospholipase D (PLD) activation, without affecting either phosphatidylinositol-phospholipase C or cytosolic phospholipase A2 (PLA2) enzymatic activity. CD16-induced secretory PLA2 (sPLA2) protein release as well as its enzymatic activity in both cell-associated and soluble forms were also found to be inhibited upon β1 integrin coengagement. The similar effects exerted by specific PLD pharmacological inhibitors (2,3- diphosphoglycerate, ethanol) suggest that in our experimental system, sPLA2 secretion and activation are under the control of a PLD-dependent pathway. By using pharmacological inhibitors (2,3-diphosphoglycerate, wortmannin, ethanol) we also demonstrated that PLD activation is an important step in the CD16-triggered signaling cascade that leads to NK cytotoxic granule exocytosis. Consistent with these findings, fibronectin receptor engagement, by either mAbs or natural ligands, resulted in a selective inhibition of CD16-triggered, but not of PMA/ionomycin-induced, degranulation that was reversed by the exogenous addition of purified PLD from Streptomyces chromofuscus.
AB - Recent data indicate that integrin-generated signals can modulate different receptor-stimulated cell functions in both a positive (costimulation) and a negative (inhibition) fashion. Here we investigated the ability of β1 integrins, namely α4β1 and α5β1 fibronectin receptors, to modulate CD16-triggered phospholipase activation in human NK cells, β1 integrin simultaneous crosslinking selectively inhibited CD16- induced phospholipase D (PLD) activation, without affecting either phosphatidylinositol-phospholipase C or cytosolic phospholipase A2 (PLA2) enzymatic activity. CD16-induced secretory PLA2 (sPLA2) protein release as well as its enzymatic activity in both cell-associated and soluble forms were also found to be inhibited upon β1 integrin coengagement. The similar effects exerted by specific PLD pharmacological inhibitors (2,3- diphosphoglycerate, ethanol) suggest that in our experimental system, sPLA2 secretion and activation are under the control of a PLD-dependent pathway. By using pharmacological inhibitors (2,3-diphosphoglycerate, wortmannin, ethanol) we also demonstrated that PLD activation is an important step in the CD16-triggered signaling cascade that leads to NK cytotoxic granule exocytosis. Consistent with these findings, fibronectin receptor engagement, by either mAbs or natural ligands, resulted in a selective inhibition of CD16-triggered, but not of PMA/ionomycin-induced, degranulation that was reversed by the exogenous addition of purified PLD from Streptomyces chromofuscus.
UR - http://www.scopus.com/inward/record.url?scp=0033558277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033558277&partnerID=8YFLogxK
M3 - Article
C2 - 9973479
AN - SCOPUS:0033558277
VL - 162
SP - 2064
EP - 2072
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -