Increased Acute Inflammation, Leukotriene B4-Induced Chemotaxis, and Signaling in Mice Deficient for G Protein-Coupled Receptor Kinase 6

Nov 25, 2003Journal of immunology (Baltimore, Md. : 1950)

Higher sudden inflammation and immune cell movement triggered by leukotriene B4 in mice lacking a specific cell signaling regulator

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Abstract

GRK6 deficiency leads to increased acute inflammatory response and prolonged signaling in neutrophils.

  • Neutrophils lacking GRK6 show heightened migration and response to LTB(4).
  • GRK6-deficient mice exhibit significantly increased ear swelling and neutrophil influx after arachidonic acid application.
  • Increased intracellular calcium levels and prolonged actin polymerization are observed in GRK6-deficient neutrophils in response to LTB(4).
  • Receptor desensitization to LTB(4) is impaired in the absence of GRK6, leading to sustained signaling.
  • Pre-exposure to LTB(4) makes both GRK6-deficient and normal neutrophils unresponsive to subsequent stimulation, indicating a different mechanism for refractory response.

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