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

Clare M. Heyworth, Mark A. Pearson, T. Michael Dexter, Gwen Wark, P. Jane Owen-lynch, Anthony D. Whetton

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Macrophage Inflammatory Protein-1α (MIP-1α can inhibit the proliferation of multipotent haemopoietic cells. Using the FDCP-Mix A4 multipotent stem cell line, MIP-1α was shown to inhibit IL-3 stimulated cell cycling (assessed using the [3H]-thymidine "suicide" assay). Furthermore MIP-1α can inhibit IL-3-stimulated [3H]-thymidine incorporation in FDCP-Mix cells, with half maximal inhibition observed at 3 ng/ml MIP-1α Prostaglandin E2, but not MlP-1α was able to elevate cyclic AMP levels in FDCP-Mix A4 cells although both agents can cause growth inhibition. However, MIP-1α addition resulted in a pertussis-toxin-insensitive increase in the level of the second messenger inositol 1,4,5 trisphosphate (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-1α and the dose dependency correlated with that for MIP-1α mediated growth inhibition. A rapid increase in cytosolic Ca2+levels was also observed in response to MIP-1α 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. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalGrowth Factors
Volume12
Issue number3
DOIs
Publication statusPublished - 1 May 1995
Externally publishedYes

Fingerprint

Macrophage Inflammatory Proteins
Inositol 1,4,5-Trisphosphate
Stem cells
Stem Cells
Interleukin-3
Cell Line
Thymidine
Growth
Pertussis Toxin
Second Messenger Systems
Inositol
Dinoprostone
Cyclic AMP
Hydrolysis
Assays
Multipotent Stem Cells
Reproductive Rights
Lipids
Suicide
Inhibition (Psychology)

Cite this

Heyworth, Clare M. ; Pearson, Mark A. ; Dexter, T. Michael ; Wark, Gwen ; Owen-lynch, P. Jane ; Whetton, Anthony D. / Macrophage inflammatory protein-1α mediated growth inhibition in a haemopoietic stem cell line is associated with inositol 1,4,5 trisphosphate generation. In: Growth Factors. 1995 ; Vol. 12, No. 3. pp. 165-172.
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Macrophage inflammatory protein-1α mediated growth inhibition in a haemopoietic stem cell line is associated with inositol 1,4,5 trisphosphate generation. / Heyworth, Clare M.; Pearson, Mark A.; Dexter, T. Michael; Wark, Gwen; Owen-lynch, P. Jane; Whetton, Anthony D.

In: Growth Factors, Vol. 12, No. 3, 01.05.1995, p. 165-172.

Research output: Contribution to journalArticle

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T1 - Macrophage inflammatory protein-1α mediated growth inhibition in a haemopoietic stem cell line is associated with inositol 1,4,5 trisphosphate generation

AU - Heyworth, Clare M.

AU - Pearson, Mark A.

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AU - Whetton, Anthony D.

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AB - Macrophage Inflammatory Protein-1α (MIP-1α can inhibit the proliferation of multipotent haemopoietic cells. Using the FDCP-Mix A4 multipotent stem cell line, MIP-1α was shown to inhibit IL-3 stimulated cell cycling (assessed using the [3H]-thymidine "suicide" assay). Furthermore MIP-1α can inhibit IL-3-stimulated [3H]-thymidine incorporation in FDCP-Mix cells, with half maximal inhibition observed at 3 ng/ml MIP-1α Prostaglandin E2, but not MlP-1α was able to elevate cyclic AMP levels in FDCP-Mix A4 cells although both agents can cause growth inhibition. However, MIP-1α addition resulted in a pertussis-toxin-insensitive increase in the level of the second messenger inositol 1,4,5 trisphosphate (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-1α and the dose dependency correlated with that for MIP-1α mediated growth inhibition. A rapid increase in cytosolic Ca2+levels was also observed in response to MIP-1α 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. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

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