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Synthetic peptide MMK-1 is a highly specific chemotactic agonist for leukocyte FPRL1

  1. Author:
    Hu, J. Y.
    Le, Y. Y.
    Gong, W. H.
    Dunlop, N. M.
    Gao, J. L.
    Murphy, P. M.
    Wang, J. M.

  2. Author Address

    NCI, Frederick Canc Res & Dev Ctr, LMI, DBS, Bldg 560, Room 31- 40, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, LMI, DBS, Frederick, MD 21702 USA. SAIC, Intramural Res Support Program, Frederick, MD USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Hunan Med Univ, Canc Res Inst, Changsha, Peoples R China. Wang JM NCI, Frederick Canc Res & Dev Ctr, LMI, DBS, Bldg 560, Room 31-40, Frederick, MD 21702 USA.
    1. Year: 2001
  2. Journal: Journal of Leukocyte Biology
    1. 70
    2. 1
    3. Pages: 155-161
  4. Type of Article: Article
  1. Abstract:

    Human phagocytic leukocytes express the seven-transmembrane G- protein-coupled receptors formyl peptide receptor (FPR) and FPR-like 1 (FPRL1). MMK-1, a synthetic peptide derived from a random peptide library, is reported to induce calcium mobilization specifically in human FPRL1 gene-transfected cells. However, its actions on human phagocytic leukocytes remain poorly defined. We found that NMK-1 is a potent chemotactic and calcium-mobilizing agonist for human monocytes, neutrophils, and FPRL1-transfected human embryonic kidney (HEK) 293 cells but is inactive in cells transfected with FPR. MMK-1 also activated HEK 293 cells transfected with FPR2, a mouse counterpart of human FPRL1. Furthermore, MMK-1 increased pertussis toxin-sensitive production of inflammatory cytokines in human monocytes. MMK-1 signaling in human phagocytes was completely desensitized by a well-defined FPRL1 agonist, suggesting that FPRL1 is likely a receptor that mediates the action of MMK-1 in primary cells. Since MMK-1 is one of the most potent FPRL1-specific agonists identified so far, it can serve as a modulator of the host defense and a useful agent for further studying the signaling and function of FPRL1.

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