Activation of the inositol phospholipid signaling system by receptors for extracellular ATP in human neutrophils, monocytes, and neutrophil/monocyte progenitor cells.
We have presented evidence indicating that P2-purinergic receptors may activate the polyphosphoinositide-phospholipase C in HL60 cells via the mediation of a pertussis-toxin-sensitive GTP-binding protein, which also mediates the actions of chemotactic peptide receptors in these and other phagocytic white blood cells. However, our data also suggest that these same receptors can be coupled to the phospholipase via an additional pertussis-toxin-insensitive mechanism. This latter finding raises the possibility that undifferentiated HL60 cells express two distinct GTP-binding proteins coupled to phospholipase C; one of these is very likely to be the GHL/GC protein recently isolated from this cell line. Significantly, the data of Oinuma et al. and Falloon et al. indicate that expression of the 40-kDa alpha-subunit/toxin substrate increases upon differentiation of HL60 cells along the granulocyte pathway. It would be interesting to determine whether expression of the putative pertussis-toxin-insensitive G-protein decreases with differentiation of these and other myelomonocytic progenitor cells. Such studies, which are now in progress, should be facilitated by the fact that the P2-purinergic receptors appear to be expressed in myelopoietic cells from the promyelocytic/promonocytic stages through the terminally differentiated stages represented by circulating neutrophils and monocytes.
Dubyak
G R
GR
Department of Physiology/Biophysics, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
Cowen
D S
DS
Lazarus
H M
HM
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D011983:Receptors, Purinergic / Q000502:physiology*
D010716:Phosphatidylinositols; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002118:Calcium