Human blood and synovial fluid neutrophils cultured in vitro undergo programmed cell death which is promoted by the addition of synovial fluid.

Inflammatory neutrophils retain susceptibility to apoptosis mediated via the Fas death receptor

“…Although absolute numbers are small, this is likely to indicate a significant excess of apoptotic deaths in the inflammatory population because apoptotic neutrophils are thought to be identifiable for only short periods of time in inflammatory exudates, before ingestion and degradation by macrophages [4,26]. Furthermore there was an accelerated rate of apoptosis after culture in vitro over 20 h. This was comparable to the accelerated in vitro apoptosis of synovial fluid neutrophils previously described by Bell et al [27] and Savill et al [2].…”

“…Fas may, however, be a physiologically relevant death signal for inflammatory neutrophils because monocyte-macrophages express high levels of FasL [32] and can induce Fas-mediated neutrophil death [28]. Moreover, sFasL is detectable in synovial fluid [33] and addition of synovial fluid to peripheral blood neutrophils has been shown to accelerate their death by apoptosis [27].…”

“…We therefore examined the induction of apoptosis by Fas ligation in inflammatory compared with peripheral blood neutrophils, and the suppression of this death by co-incubation with a neutrophil survival factor. We chose GM-CSF because it inhibits both constitutive [7,8] and Fas-mediated [37] apoptosis of peripheral blood neutrophils and has been identified in vivo, both in synovial fluid samples from inflamed rheumatoid joints [27,38] and in lung lavage fluid from ARDS patients [12]. Induction of neutrophil apoptosis by Fas ligation is an attractive therapeutic strategy, by analogy with ligation of Fas on airway eosinophils, which has been shown to accelerate eosinophil apoptosis and to abrogate airway inflammation in an animal model of allergic inflammation [15].…”

Apoptosis in the rheumatic diseases

“…Neutrophils isolated from RA joints spontaneously undergo programmed cell death in vitro with the same kinetics as those from peripheral blood (70), and evidence of phagocytosis by macrophages has been reported (24,71). It is unknown whether macrophage phagocytosis of apoptotic neutrophils is sufficient to remove all of these cells and whether there are any pathologic consequences of this process.…”

How Important are Innate Immunity Cells in Osteoarthritis Pathology

“…Reports about apoptosis of neutrophils in OA are few and controversial. Bell et al showed that synovial fluid from OA patients contains factors inhibiting neutrophil survival (Bell et al, 1995). There is also a hypothesis that pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals present in the OA joint fluid and tissue can activate Ca2+ signal in neutrophils thereby prolonging their survival and reducing their apoptosis (Rosenthal, 2011).…”