Participation of non-receptor Src family tyrosine kinases in the formation of neutrophil extracellular traps

Abstract

Neutrophils release decondensed nuclear chromatin or Neutrophil Extracellular Traps (NETs) in response to a great number of physiological and pharmacological stimuli. However, apart from the host defensive function, NETs play an essential role in the pathogenesis of various autoimmune, inflammatory, and malignant diseases. Therefore, understanding the molecular mechanisms of NETs formation, usually leading to the neutrophil death (NETosis), is important to control the probable aberrant or excessive NETs release. The Src-family kinases (Src-kinases) are non-receptor tyrosine kinases that are involved in a variety of human functions. However, their role in NETosis and oxidative burst has not been sufficiently studied. Since three representatives of Src-kinases (Hck, Fgr, and Lyn) have been described in human neutrophils, we studied their contribution to NETosis and oxidative burst using inhibitory analysis. We have shown that Src-kinases are involved in the oxidative burst and NETosis induced by the calcium ionophore A23187 but not the mimetic of diacylglycerol phorbol-12-myristate-13-acetate (PMA).