title: Protein kinase C-θ is required for murine neutrophil recruitment and adhesion strengthening under flow.
abstract: 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.
authors.affiliation: Department of Nephrology and Hypertensiology, Hannover Medical School, 30625 Hannover, Germany. bertram.anna@mh-hannover.de
authors.forename: Anna
authors.initials: A
authors.lastname: Bertram
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Sibylle
authors.initials: S
authors.lastname: von Vietinghoff
authors.forename: Carmen
authors.initials: C
authors.lastname: de Pablo
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Nelli
authors.initials: N
authors.lastname: Shushakova
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion; D054360:Chemokine CXCL1 / Q000494:pharmacology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D054992:Immunological Synapses; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018715:Microscopy, Video; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000074121:Protein Kinase C-theta; D014699:Venules / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D018821:CD18 Antigens; D054360:Chemokine CXCL1; D007527:Isoenzymes; D016169:Lymphocyte Function-Associated Antigen-1; D049452:Green Fluorescent Proteins; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta