Regulation of Neutrophil Apoptosis Differs after in vivo Transmigration to Skin Chambers and Synovial Fluid: A Role for Inflammasome-Dependent Interleukin-1 beta Release

• 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)-1 beta which delays neutrophil apoptosis. Contrary to skin chamber fluid, synovial fluid from patients with rheumatic arthritis contained only moderate levels of IL-1 beta, 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-1 beta signaling could be an important factor in determining how life and death of neutrophils is regulated in inflamed tissues.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Nyckelord

Phagocyte

Granulocyte

Apoptosis

Transmigration

Skin chamber

Exudate

Rheumatoid arthritis

programmed cell-death

rheumatoid-arthritis

activation

mobilization

clearance

cytokines

survival

hypoxia

blood

vitro

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)