Protein kinase C-θ is required for murine neutrophil recruitment and adhesion strengthening under flow

J Immunol. 2012 Apr 15;188(8):4043-51. doi: 10.4049/jimmunol.1101651. Epub 2012 Mar 7.


Protein kinase C (PKC)-θ is involved in T cell activation via regulating the avidity of the β(2) integrin LFA-1 in the immunological synapse. LFA-1 also mediates leukocyte adhesion. To investigate the role of PKC-θ in neutrophil adhesion, we performed intravital microscopy in cremaster venules of mice reconstituted with bone marrow from LysM-GFP(+) (wild-type [WT]) and PKC-θ gene-deficient (Prkcq(-/-)) mice. Following stimulation with CXCL1, both WT and Prkcq(-/-) cells became adherent. Although most WT neutrophils remained adherent for at least 180 s, 50% of Prkcq(-/-) neutrophils were detached after 105 s and most by 180 s. Upon CXCL1 injection, rolling of all WT neutrophils stopped for 90 s, but rolling of Prkcq(-/-) neutrophils started 30 s after CXCL1 stimulation. A similar neutrophil adhesion defect was seen in vitro, and spreading of Prkcq(-/-) neutrophils was delayed. Prkcq(-/-) neutrophil recruitment was impaired in fMLP-induced transmigration into the cremaster muscle, thioglycollate-induced peritonitis, and LPS-induced lung injury. We conclude that PKC-θ mediates integrin-dependent neutrophil functions and is required to sustain neutrophil adhesion in postcapillary venules in vivo. These findings suggest that the role of PKC-θ in outside-in signaling following engagement of neutrophil integrins is relevant for inflammation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD18 Antigens / genetics
  • CD18 Antigens / immunology*
  • Cell Adhesion
  • Chemokine CXCL1 / pharmacology
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Immunological Synapses
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / immunology*
  • Lymphocyte Activation
  • Lymphocyte Function-Associated Antigen-1 / genetics
  • Lymphocyte Function-Associated Antigen-1 / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Video
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Neutrophils / physiology
  • Protein Kinase C / deficiency
  • Protein Kinase C / genetics
  • Protein Kinase C / immunology*
  • Protein Kinase C-theta
  • Venules / cytology
  • Venules / immunology*
  • Venules / metabolism


  • CD18 Antigens
  • Chemokine CXCL1
  • Isoenzymes
  • Lymphocyte Function-Associated Antigen-1
  • Green Fluorescent Proteins
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta