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

Anna Bertram, Hong Zhang, Sibylle Von Vietinghoff, Carmen De Pablo, Hermann Haller, Nelli Shushakova, Klaus Ley

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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 genedeficient (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.

Original languageEnglish (US)
Pages (from-to)4043-4051
Number of pages9
JournalJournal of Immunology
Issue number8
StatePublished - Apr 15 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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