Correlation Engine 2.0
Clear Search sequence regions


  • actin (1)
  • antigen (3)
  • CD11 (1)
  • CD18 (1)
  • CXCL1 (3)
  • function (3)
  • HPK1 (12)
  • humans (1)
  • icam 1 (1)
  • kinases (1)
  • lamellipodium (1)
  • LFA 1 (4)
  • lymphocyte (3)
  • mAbp1 (3)
  • Mac- 1 (1)
  • mice (5)
  • mice knockout (1)
  • neutrophil (10)
  • phase (1)
  • protein- kinases (1)
  • tumor necrosis factor α (1)
  • β2 integrins (3)
  • Sizes of these terms reflect their relevance to your search.

    Recruitment of polymorphonuclear neutrophils (PMNs) to sites of acute inflammation critically depends on β2 integrins (CD11/CD18). Recently, the mammalian actin-binding protein 1 (mAbp1) was identified as an important adaptor protein regulating PMN trafficking downstream of β2 integrins. Here, we show that mAbp1 constitutively co-immunoprecipitated with hematopoietic progenitor kinase 1 (HPK1) in neutrophil-like differentiated HL-60 (dHL-60) cells. HPK1 was enriched at the lamellipodium of polarized dHL-60 cells, where it colocalized with mAbp1 and actin. Functional analysis of PMNs from HPK1-deficient mice showed that HPK1 was critical for CXCL1-induced lymphocyte function-associated antigen 1 (LFA-1)-mediated PMN adhesion to ICAM-1 under flow conditions. Accordingly, CXCL1-mediated induction of high-affinity LFA-1 required HPK1, but macrophage antigen 1 (Mac-1) affinity regulation was independent of HPK1. Intravital microscopy of the mouse cremaster muscle confirmed the defect of CXCL1-induced leukocyte adhesion in HPK1-deficient mice. Furthermore, β2 integrin-mediated post-adhesion processes-adhesion strengthening, spreading, and directed mechanotactic crawling of PMNs under flow conditions-involved HPK1 in vitro and in vivo. Upon intrascrotal administration of tumor necrosis factor α (TNF-α), PMN adhesion and extravasation were severely compromised in HPK1-deficient mice. In summary, our results indicate that HPK1 is critically involved in LFA-1-mediated PMN trafficking during acute inflammation.

    Citation

    Sascha M Jakob, Robert Pick, Doris Brechtefeld, Claudia Nussbaum, Friedemann Kiefer, Markus Sperandio, Barbara Walzog. Hematopoietic progenitor kinase 1 (HPK1) is required for LFA-1-mediated neutrophil recruitment during the acute inflammatory response. Blood. 2013 May 16;121(20):4184-94

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 23460610

    View Full Text