Biological and structural properties of MIP-1 alpha expressed in yeast.
AffiliationBritish Bio-technology, Cowley, Oxford.
MetadataShow full item record
AbstractThe 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).
CitationBiological and structural properties of MIP-1 alpha expressed in yeast. 1992, 4 (1):76-82 Cytokine
- Macrophage inflammatory protein (MIP)-1 beta abrogates the capacity of MIP-1 alpha to suppress myeloid progenitor cell growth.
- Authors: Broxmeyer HE, Sherry B, Cooper S, Ruscetti FW, Williams DE, Arosio P, Kwon BS, Cerami A
- Issue date: 1991 Oct 15
- Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells. Interacting effects involving suppression, synergistic suppression, and blocking of suppression.
- Authors: Broxmeyer HE, Sherry B, Cooper S, Lu L, Maze R, Beckmann MP, Cerami A, Ralph P
- Issue date: 1993 Apr 15
- Distinct and overlapping direct effects of macrophage inflammatory protein-1 alpha and transforming growth factor beta on hematopoietic progenitor/stem cell growth.
- Authors: Keller JR, Bartelmez SH, Sitnicka E, Ruscetti FW, Ortiz M, Gooya JM, Jacobsen SE
- Issue date: 1994 Oct 1
- Interferon-inducible protein 10 and macrophage inflammatory protein-1 alpha inhibit growth factor stimulation of Raf-1 kinase activity and protein synthesis in a human growth factor-dependent hematopoietic cell line.
- Authors: Aronica SM, Mantel C, Gonin R, Marshall MS, Sarris A, Cooper S, Hague N, Zhang XF, Broxmeyer HE
- Issue date: 1995 Sep 15
- Induction of murine peritoneal macrophage colony-forming cells by peritoneal administration of macrophage inflammatory protein-1 alpha.
- Authors: Chen B, Chou TH, Sensenbrenner L
- Issue date: 1993 Nov