Macrophage inflammatory protein-1 alpha mediated growth inhibition in a haemopoietic stem cell line is associated with inositol 1,4,5 triphosphate generation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97481
Title:
Macrophage inflammatory protein-1 alpha mediated growth inhibition in a haemopoietic stem cell line is associated with inositol 1,4,5 triphosphate generation.
Authors:
Heyworth, Clare M; Pearson, Mark A; Dexter, T Michael; Wark, G; Owen-Lynch, P J; Whetton, Anthony D
Abstract:
Macrophage Inflammatory Protein-1 alpha (MIP-1 alpha) can inhibit the proliferation of multipotent haemopoietic cells. Using the FDCP-Mix A4 multipotent stem cell line, MIP-1 alpha was shown to inhibit 1L-3 stimulated cell cycling (assessed using the [3H]-thymidine "suicide" assay). Furthermore, MIP-1 alpha can inhibit 1L-3-stimulated [3H]-thymidine incorporation in FDCP-Mix cells, with half maximal inhibition observed at 3 ng/ml MIP-1 alpha. Prostaglandin E2, but not MIP-1 alpha was able to elevate cyclic AMP levels in FDCP-Mix A4 cells although both agents can cause growth inhibition. However, MIP-1 alpha addition resulted in a pertussis-toxin-insensitive increase in the level of the second messenger inositol 1,4,5 triphosphate (Ins 1,4,5P3). This response was both rapid (maximal at 5 seconds) and transient. A half maximal effect was observed at 5 ng/ml MIP-1 alpha and the dose dependency correlated with that for MIP-1 alpha mediated growth inhibition. A rapid increase in cytosolic Ca2+ levels was also observed in response to MIP-1 alpha. Inositol lipid hydrolysis and an increase in cytosolic Ca2+ (signals normally associated with proliferation) may therefore be implicated in growth inhibitory mechanisms in multipotent cells.
Affiliation:
Department of Experimental Haematology, Paterson Institute, Manchester, UK.
Citation:
Macrophage inflammatory protein-1 alpha mediated growth inhibition in a haemopoietic stem cell line is associated with inositol 1,4,5 triphosphate generation. 1995, 12 (3):165-72 Growth Factors
Journal:
Growth Factors
Issue Date:
1995
URI:
http://hdl.handle.net/10541/97481
DOI:
10.3109/08977199509036876
PubMed ID:
8619922
Type:
Article
Language:
en
ISSN:
0897-7194
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorPearson, Mark Aen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorWark, Gen
dc.contributor.authorOwen-Lynch, P Jen
dc.contributor.authorWhetton, Anthony Den
dc.date.accessioned2010-04-27T13:29:10Z-
dc.date.available2010-04-27T13:29:10Z-
dc.date.issued1995-
dc.identifier.citationMacrophage inflammatory protein-1 alpha mediated growth inhibition in a haemopoietic stem cell line is associated with inositol 1,4,5 triphosphate generation. 1995, 12 (3):165-72 Growth Factorsen
dc.identifier.issn0897-7194-
dc.identifier.pmid8619922-
dc.identifier.doi10.3109/08977199509036876-
dc.identifier.urihttp://hdl.handle.net/10541/97481-
dc.description.abstractMacrophage Inflammatory Protein-1 alpha (MIP-1 alpha) can inhibit the proliferation of multipotent haemopoietic cells. Using the FDCP-Mix A4 multipotent stem cell line, MIP-1 alpha was shown to inhibit 1L-3 stimulated cell cycling (assessed using the [3H]-thymidine "suicide" assay). Furthermore, MIP-1 alpha can inhibit 1L-3-stimulated [3H]-thymidine incorporation in FDCP-Mix cells, with half maximal inhibition observed at 3 ng/ml MIP-1 alpha. Prostaglandin E2, but not MIP-1 alpha was able to elevate cyclic AMP levels in FDCP-Mix A4 cells although both agents can cause growth inhibition. However, MIP-1 alpha addition resulted in a pertussis-toxin-insensitive increase in the level of the second messenger inositol 1,4,5 triphosphate (Ins 1,4,5P3). This response was both rapid (maximal at 5 seconds) and transient. A half maximal effect was observed at 5 ng/ml MIP-1 alpha and the dose dependency correlated with that for MIP-1 alpha mediated growth inhibition. A rapid increase in cytosolic Ca2+ levels was also observed in response to MIP-1 alpha. Inositol lipid hydrolysis and an increase in cytosolic Ca2+ (signals normally associated with proliferation) may therefore be implicated in growth inhibitory mechanisms in multipotent cells.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshCalcium-
dc.subject.meshCell Division-
dc.subject.meshCell Line-
dc.subject.meshChemokine CCL4-
dc.subject.meshColony-Forming Units Assay-
dc.subject.meshCyclic AMP-
dc.subject.meshCytosol-
dc.subject.meshDNA-
dc.subject.meshDinoprostone-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshGrowth Inhibitors-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshInositol 1,4,5-Trisphosphate-
dc.subject.meshInterleukin-3-
dc.subject.meshKinetics-
dc.subject.meshMacrophage Inflammatory Proteins-
dc.subject.meshMice-
dc.subject.meshMonokines-
dc.subject.meshPertussis Toxin-
dc.subject.meshS Phase-
dc.subject.meshSignal Transduction-
dc.subject.meshThymidine-
dc.subject.meshVirulence Factors, Bordetella-
dc.titleMacrophage inflammatory protein-1 alpha mediated growth inhibition in a haemopoietic stem cell line is associated with inositol 1,4,5 triphosphate generation.en
dc.typeArticleen
dc.contributor.departmentDepartment of Experimental Haematology, Paterson Institute, Manchester, UK.en
dc.identifier.journalGrowth Factorsen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.