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PMID:16873675
| Citation |
Lehman, N, Di Fulvio, M, McCray, N, Campos, I, Tabatabaian, F and Gomez-Cambronero, J (2006) Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2. Blood 108:3564-72 |
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| Abstract |
We have investigated whether the signaling protein phospholipase D is implicated in leukocyte cell motility. Treating differentiated HL-60 cells with small interfering RNAs (siRNAs), to deplete endogenous expression of the PLD1 isoform, led to an abolishment of basal chemokinesis that could not be rescued with chemoattractants ENA-78, FMLP, and IL-8. Transient overexpression of PLD1 increased both chemokinesis and chemotaxis toward IL-8 and FMLP but not toward ENA-78. Chemokinesis was not mediated by the enzymatic activity of PLD1, but the chemotactic response was, because a lipase-inactive mutant (PLD1-K830R) negated all chemokine-induced potentiating actions and because IL-8 and FMLP increased activity in vitro. Gene expression silencing of the other mammalian isoform, PLD2, also led to cell migration arrest, whereas ENA-78 selectively increased endogenous PLD2 activity and chemotaxis of HL-60 cells overexpressing a myc-pcDNA-PLD2 construct. Thus, PLD1 is differentially activated by CXCR-1, whereas CXCR-2 (and possibly CXCR-1) mediates PLD2 activation. Finally, immunofluorescence microscopy showed that both isoforms were associated with cell polarity and directionality concomitantly with adhesion and F-actin polymerization in response to IL-8. These data represent the first demonstration of the involvement of PLD and its enzymatic activity toward chemokines in the key physiologic process of leukocyte migration. |
| Links |
PubMed PMC1895436 Online version:10.1182/blood-2006-02-005959 |
| Keywords |
Cell Adhesion; Cell Movement/drug effects; Cell Polarity; Chemotaxis, Leukocyte/drug effects; HL-60 Cells; Humans; Interleukin-8/pharmacology; N-Formylmethionine Leucyl-Phenylalanine/pharmacology; Neutrophils/physiology; Phagocytes/physiology; Phospholipase D/physiology; RNA, Small Interfering/pharmacology; Receptors, Interleukin-8A/physiology; Receptors, Interleukin-8B/physiology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0090023: positive regulation of neutrophil chemotaxis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Figure 1D shows the PLD1-siRNAs decreased cell migration Figure 2A shows the overexpression of PLD1 increases cell chemotaxis. Figure 3C shows that an PLD1 enzyme-inactive mutant has decreased chemotaxis when compared to wild type PLD1 activity. |
complete | ||||
| GO:0031668: cellular response to extracellular stimulus |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Figure 4A: Showed PLD1 activity increased as cell migration increased with presence of chemoattractants. FIgure 4B and C: Showed how cell migration decreased in the presence of PLD1 inhibitors even in the presence of chemoattractants. |
complete | ||||
| GO:0002687: positive regulation of leukocyte migration |
ECO:0000315: |
P |
Figure 5D: Showed increased cell migration due to chemoattractants. Figure 5E: Showed that silencing PLD2 significantly decreased the cell migration to the chemoattractants. |
complete | ||||
See also
References
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