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

Heyworth, C M and Pearson, M A and Dexter, T M and Wark, G and Owen-Lynch, P J and Whetton, A D (1995) Macrophage inflammatory protein-1 alpha mediated growth inhibition in a haemopoietic stem cell line is associated with inositol 1,4,5 triphosphate generation. Growth factors (Chur, Switzerland), 12 (3). pp. 165-172. ISSN 0897-7194

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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.

Item Type: Article
Journal or Publication Title: Growth factors (Chur, Switzerland)
Uncontrolled Keywords: MIP-1α ; growth inhibition ; FDCP-Mix ; inositol lipid hydrolysis
Subjects: Q Science > QR Microbiology
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 56087
Deposited By: ep_importer_pure
Deposited On: 24 Jul 2012 11:44
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 20:46
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/56087

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