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Critical role of phospholipase C2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis

¹ Department of Physiology, Semmelweis University School of Medicine, 1094 Budapest, Hungary
² Department of Neonatology, University Children's Hospital, 69120 Heidelberg, Germany
³ Walter Brendel Center of Experimental Medicine, Ludwig-Maximilians-University, 81377 Munich, Germany

CORRESPONDENCE Attila Mócsai: mocsai{at}eok.sote.hu

β₂ integrins and Fc receptors are critically involved in neutrophil activation at the site of inflammation. Both receptor types trigger a receptor-proximal tyrosine phosphorylation cascade through Src family kinases and Syk, but further downstream signaling events are poorly understood. We show that phospholipase C (PLC) 2 is phosphorylated downstream of Src family kinases and Syk during integrin or Fc receptor-mediated activation of neutrophils. PLC2^–/– neutrophils are completely defective in β₂ integrin or Fc receptor-mediated functional responses such as respiratory burst, degranulation, or cell spreading in vitro and show reduced adhesion/spreading in inflamed capillary venules in vivo. However, PLC2^–/– neutrophils respond normally to various other agonists, including chemokines, bacterial formyl peptides, Toll-like receptor ligands, or proinflammatory cytokines, and migrate normally both in vitro and in vivo. To confirm the in vivo relevance of these observations, the effect of the PLC2^–/– mutation was tested in the K/BxN serum transfer arthritis model, which is known to require β₂ integrins, Fc receptors, and neutrophils. PLC2 deficiency completely protected mice from clinical signs and histological features of arthritis as well as from arthritis-induced loss of articular function. These results identify PLC2 as a critical player of integrin and Fc receptor-mediated neutrophil functions and the neutrophil-mediated effector phase of autoimmune arthritis.

© 2009 Jakus et al.
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This article has been cited by other articles:

• Jakus, Z., Simon, E., Frommhold, D., Sperandio, M., Mocsai, A. (2009). Critical role of phospholipase C{gamma}2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis. JCB 184: i15-i15 [Full Text]  

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