Catlyn Blanchard

Publications (2)35.69 Total impact

• Source

  Available from: PubMed Central

  Article: Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling.

  Amit Prasad, Yonghui Jia, Anutosh Chakraborty, Yitang Li, Supriya K Jain, Jia Zhong, Saurabh Ghosh Roy, Fabien Loison, Subhanjan Mondal, Jiro Sakai, Catlyn Blanchard, Solomon H Snyder, Hongbo R Luo
  [show abstract] [hide abstract]
  ABSTRACT: Inositol phosphates are widely produced throughout animal and plant tissues. Diphosphoinositol pentakisphosphate (InsP7) contains an energetic pyrophosphate bond. Here we demonstrate that disruption of inositol hexakisphosphate kinase 1 (InsP6K1), one of the three mammalian inositol hexakisphosphate kinases (InsP6Ks) that convert inositol hexakisphosphate (InsP6) to InsP7, conferred enhanced phosphatidylinositol-(3,4,5)-trisphosphate (PtdIns(3,4,5)P3)-mediated membrane translocation of the pleckstrin homology domain of the kinase Akt and thus augmented downstream PtdIns(3,4,5)P3 signaling in mouse neutrophils. Consequently, these neutrophils had greater phagocytic and bactericidal ability and amplified NADPH oxidase-mediated production of superoxide. These phenotypes were replicated in human primary neutrophils with pharmacologically inhibited InsP6Ks. In contrast, an increase in intracellular InsP7 blocked chemoattractant-elicited translocation of the pleckstrin homology domain to the membrane and substantially suppressed PtdIns(3,4,5)P3-mediated cellular events in neutrophils. Our findings establish a role for InsP7 in signal transduction and provide a mechanism for modulating PtdIns(3,4,5)P3 signaling in neutrophils.
  Nature Immunology 06/2011; 12(8):752-60. · 26.01 Impact Factor
• Source

  Available from: Sung-Yun Pai

  Article: Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis.

  Hidenori Hattori, Kulandayan K Subramanian, Jiro Sakai, Yonghui Jia, Yitang Li, Timothy F Porter, Fabien Loison, Bara Sarraj, Anongnard Kasorn, Hakryul Jo, Catlyn Blanchard, Dorothy Zirkle, Douglas McDonald, Sung-Yun Pai, Charles N Serhan, Hongbo R Luo
  [show abstract] [hide abstract]
  ABSTRACT: Neutrophil chemotaxis plays an essential role in innate immunity, but the underlying cellular mechanism is still not fully characterized. Here, using a small-molecule functional screening, we identified NADPH oxidase-dependent reactive oxygen species as key regulators of neutrophil chemotactic migration. Neutrophils with pharmacologically inhibited oxidase, or isolated from chronic granulomatous disease (CGD) patients and mice, formed more frequent multiple pseudopodia and lost their directionality as they migrated up a chemoattractant concentration gradient. Knocking down NADPH oxidase in differentiated neutrophil-like HL60 cells also led to defective chemotaxis. Consistent with the in vitro results, adoptively transferred CGD murine neutrophils showed impaired in vivo recruitment to sites of inflammation. Together, these results present a physiological role for reactive oxygen species in regulating neutrophil functions and shed light on the pathogenesis of CGD.
  Proceedings of the National Academy of Sciences 02/2010; 107(8):3546-51. · 9.68 Impact Factor