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Biological and structural properties of MIP-1 alpha expressed in yeast.
Clements, J M Craig, S Gearing, A J Hunter, M G Heyworth, Clare M Dexter, T Michael Lord, Brian I
Clements, J M
Craig, S
Gearing, A J
Hunter, M G
Heyworth, Clare M
Dexter, T Michael
Lord, Brian I
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Abstract
The murine macrophage inflammatory proteins-1 alpha (MIP-1 alpha) and MIP-1 beta are distinct but closely related cytokines. Partially purified mixtures of the two proteins affect neutrophil function and cause local inflammation and fever. The particular properties of MIP-1 alpha have not been well studied, although it has been identified as being identical to an inhibitor of haemopoietic stem cell growth. We have expressed MIP-1 alpha in yeast cells and purified it to sequence homogeneity. Structural analysis of this biologically active material by circular dichroism and fluorescence spectroscopy confirms that MIP-1 alpha has a very similar secondary and tertiary structure to platelet factor 4 and interleukin 8 with which it shares limited sequence homology. The in-vitro stem cell inhibitory properties have been confirmed using a range of murine progenitor cells including purified bone marrow progenitor cells (FACS-1), the FDCP-mix A4 cell line, and spleen colony forming unit (CFU-S) populations. Plateau levels of inhibition of stem cell growth were achieved using concentrations of 0.15 micrograms/ml MIP-1 alpha. We have also demonstrated that MIP-1 alpha is active in vivo: 5 micrograms of MIP-1 alpha per mouse given as a bolus injection, protects stem cells from subsequent in-vitro killing by tritiated thymidine. MIP-1 alpha was also shown to enhance the proliferation of more committed progenitor granulocyte macrophage-colony forming cells (GM-CFC) in response to granulocyte macrophage-colony stimulating factor (GM-CSF).
Affiliation
Description
Date
1992-01
Publisher
Collections
Keywords
Haematopoietic Stem Cells
Type
Article
Citation
Biological and structural properties of MIP-1 alpha expressed in yeast. 1992, 4 (1):76-82 Cytokine