title: Regulation of neutrophil apoptosis differs after in vivo transmigration to skin chambers and synovial fluid: a role for inflammasome-dependent interleukin-1β release.
abstract: Short-lived neutrophils are major players in inflammation, arriving early to infected and/or injured tissues. After performed duty, neutrophils are programmed to die by apoptosis and are thereafter rapidly cleared by other phagocytes. In vitro, modulation of the apoptotic process has been thoroughly investigated in neutrophils isolated from peripheral blood, but less is known about the regulation of this process in neutrophils derived from extravascular tissues. We recently demonstrated that neutrophils having transmigrated in vivo, obtained from experimental skin chambers of healthy human subjects, are resistant to the death-delaying signals induced by a range of antiapoptotic stimuli. In the current study, we show that skin chamber neutrophils spontaneously secrete high levels of antiapoptotic interleukin (IL)-1β which delays neutrophil apoptosis. Contrary to skin chamber fluid, synovial fluid from patients with rheumatic arthritis contained only moderate levels of IL-1β, and neutrophils taken from this site were fully responsive to antiapoptotic stimulation during in vitro culture. Our data demonstrate that resistance to antiapoptotic stimulation is not a general feature of tissue neutrophils and imply that autocrine IL-1β signaling could be an important factor in determining how life and death of neutrophils is regulated in inflamed tissues.
authors.affiliation: The Phagocyte Research Laboratory, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. karin.christenson@rheuma.gu.se
authors.forename: Karin
authors.initials: K
authors.lastname: Christenson
authors.forename: Lena
authors.initials: L
authors.lastname: Björkman
authors.forename: Anna
authors.initials: A
authors.lastname: Karlsson
authors.forename: Johan
authors.initials: J
authors.lastname: Bylund
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D019898:Autocrine Communication; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology*; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology; D055815:Young Adult
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta