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Proteolytic Cleavage and Activation of Pro-Macrophage-Stimulating Protein and Upregulation of Its Receptor in Tissue Injury

  1. Author:
    Nanney, L. B.
    Skeel, A.
    Luan, J.
    Polis, S.
    Richmond, A.
    Wang, M. H.
    Leonard, E. J.

  2. Author Address

    Nanney LB VANDERBILT UNIV SCH MED DEPT PLAST SURG S-2221 MED CTR N NASHVILLE, TN 37232 USA VANDERBILT UNIV SCH MED DEPT CELL BIOL NASHVILLE, TN 37232 USA VANDERBILT UNIV SCH MED DEPT MED DERMATOL NASHVILLE, TN 37232 USA DEPT VET AFFAIRS NASHVILLE, TN USA NCI IMMUNOBIOL LAB IMMUNOPATHOL SECT FREDERICK, MD 21701 USA
    1. Year: 1998
  2. Journal: Journal of Investigative Dermatology
    1. 111
    2. 4
    3. Pages: 573-581
  4. Type of Article: Article
  1. Abstract:

    Macrophage stimulating protein (MSP) exists in blood as inactive pro-MSP. Cleavage yields active MSP, the ligand for a membrane receptor (RON) that is expressed on keratinocytes as well as macrophages, Because both cells have roles in tissue injury, we looked for active MSP and expressed RON in wounds. Concentration of pro-MSP + MSP in wound exudates was in the range for optimal activity. Western blot showed that MSP comprised about half the total, in contrast to less than 10% of the total in blood plasma. The presence of MSP was attributed to an exudate pro-MSP convertase that had an inhibitor profile consistent with a trypsin-like serine protease. Exudate evoked morphologic changes in macrophages in vitro like that of MSP. Removal of this activity by an anti-MSP column shows that exudate stimulation of macrophages is due to MSP. RON was infrequently detected in normal skin. RON protein was markedly upregulated in burn wound epidermis and accessory structures, in proliferating cells or differentiated cells, or both. RON was also detected on macrophages and capillaries. Tissue injury leads to cleavage of pro-MSP to MSP, which has potential to act on keratinocytes, macrophages, and capillaries, all components of the wound healing response. [References: 32]

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