Macrophage Inflammatory Protein-1&alpha: An Inhibitor of Clonogenic Epidermal Keratinocyte Proliferation

Abstract

Chemokines display a wide range of diverse functions and MIP-1alpha is no exception. It is not only a potent inflammatory molecule but also an inhibitor of primitive haemopoietic cell proliferation. The studies described in this thesis focus on the activity of MIP-1alpha on keratinocyte proliferation. These experiments have shown that a pure form of MIP-1alpha, derived from COS 7 cells by transient transfection, inhibits the proliferation of clonogenic human epidermal keratinocytes in vitro. This activity is fully reversible by specific anti- MIP-1alpha polyclonal antibodies. Despite this, the pure bacterial recombinant preparation of MIP-1alpha is largely inactive. In order to investigate this discrepancy, studies analysing the difference between these two MIP-1alpha preparations have been carried out. These studies suggest that the activation of the keratinocyte inhibitory function of MIP-1alpha results through a subtle structural modification which may involve the truncation of the amino-terminal amino acids. The potential role of MIP-1alpha in epithelial tissues in vivo is also discussed

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