Physiologic Concentrations of HMGB1 Have No Impact on Cytokine-Mediated Eosinophil Survival or Chemotaxis in Response to Eotaxin-2 (CCL24)

HMGB1 is an alarmin that can stimulate the innate immune system alone or in a complex with other inflammatory mediators. Given the recent interest in HMGB1 with respect to the pathogenesis of eosinophil-associated disorders, including asthmatic inflammation and chronic rhinosinusitis, we have explored the role of this mediator and in promoting eosinophil activation. HMGB1 receptors RAGE and TLR4 but not TLR2 were detected on freshly isolated human eosinophils from healthy donors. Physiologic and relevant pathophysiologic levels of biologically-active HMGB1 had no effect on survival of human eosinophils alone or in combination with pro-survival cytokines IL-5, IL-3, or GM-CSF, and increasing concentrations of HMGB1 had no impact on surface expression of RAGE, TLR2 or TLR4. Similarly, HMGB1 did not elicit chemotaxis of human eosinophils alone and had no effect in combination with the eosinophil chemotactic agent, eotaxin-2 (CCL24). However, surface expression of TLR2 and TLR4 increased in response to cell stress, notably on eosinophils that remain viable after 48 hours without IL-5. As such, HMGB1 signaling on eosinophils may be substantially more detailed, and may involve complex immunostimulatory pathways other than or in addition to those evaluated here.