CRP/anti-CRP antibodies assembly on the surfaces of cell remnants switches their phagocytic clearance toward inflammation.

Frontiers in Immunology
Christina JankoMartin Herrmann

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by the production of autoantibodies, formation of immune complexes (IC), and activation of complement that ultimately fuel acute and/or chronic inflammation. Accumulation in blood and tissues of post-apoptotic remnants is considered of etiological and pathological importance for patients with SLE. Besides receptors directly recognizing apoptotic cells, soluble opsonins of the innate immune system bind apoptotic material dependent on the stage of apoptosis. We describe the binding to the surface of secondary necrotic cells (SNEC) of the serum opsonin CRP and further opsonins. We show that anti-dsDNA and anti-CRP autoantibodies bind and sensitize SNEC. Autoantibody-sensitized SNEC were cleared by macrophages in vitro and induced a pro-inflammatory cytokine response. In conclusion, anti-CRP, CRP, and SNEC form a ternary pyrogen endowed with strong pro-inflammatory capabilities which is able to maintain and perpetuate chronic inflammation.

Citations

Oct 30, 2013·ISRN Inflammation·Terry W Du Clos
Feb 24, 2016·Frontiers in Immunology·Aparna MahajanLuis E Muñoz
Aug 20, 2015·Nature Immunology·Sanja Arandjelovic, Kodi S Ravichandran
Apr 23, 2013·Autoimmunity·Stephan MatteckaAhmed Sheriff
Nov 27, 2014·Frontiers in Immunology·Stanley Gititu KimaniRaymond B Birge
Nov 23, 2016·Nature Reviews. Rheumatology·George C TsokosKathleen E Sullivan
Dec 26, 2015·Arthritis Research & Therapy·Satu Sinikka PesickovaVladimir Tesar
Feb 3, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sophia Thanei, Marten Trendelenburg
Oct 14, 2017·Immunological Reviews·Luis E MuñozMartin Herrmann
Apr 4, 2019·Frontiers in Immunology·Bhargavi Duvvuri, Christian Lood

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Methods Mentioned

BETA
density gradient centrifugation
flow-cytometry
fluorescence microscopy
density-gradient centrifugation
FCS
ELISA

Software Mentioned

- Statistics
SPSS

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis