Insight into Neutrophil Extracellular Traps through Systematic Evaluation of Citrullination and Peptidylarginine Deiminases

Joint Authors

Holmes, Caitlyn L.
Shim, Daeun
Kernien, John
Johnson, Chad J.
Nett, Jeniel E.
Shelef, Miriam A.

Source

Journal of Immunology Research

Issue

Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2019-03-12

Country of Publication

Egypt

No. of Pages

11

Main Subjects

Biology

Abstract EN

In rheumatoid arthritis, an autoimmune inflammatory arthritis, citrullinated proteins are targeted by autoantibodies and thus thought to drive disease.

Neutrophil extracellular traps (NETs) are a source of citrullinated proteins and are increased in rheumatoid arthritis and therefore also implicated in disease pathogenesis.

However, not all NETs are citrullinated.

One theory aiming to clarify the intersection of citrullination, NETs, and rheumatoid arthritis suggests that specific stimuli induce different types of NETs defined by citrullination status.

However, most studies do not evaluate uncitrullinated NETs, only citrullinated or total NETs.

Further, the requirement for peptidylarginine deiminase (PAD) 2 and 4, two important citrullinating enzymes in neutrophils and rheumatoid arthritis, in the formation of different NETs has not been clearly defined.

To determine if specific stimulants induce citrullinated or uncitrullinated NETs and if those structures require PAD2 or PAD4, human and murine neutrophils, including from PAD4-/- and PAD2-/- mice, were stimulated in vitro and NETs imaged and quantified.

In humans, phorbol myristate acetate (PMA), ionomycin, monosodium urate (MSU), and Candida albicans induced NETs with MSU and C.

albicans inducing primarily citrullinated, PMA primarily uncitrullinated, and ionomycin a mix of NETs.

Only ionomycin and C.

albicans were strong inducers of NETs in mice with ionomycin-induced NETs mostly citrullinated and C.

albicans-induced NETs a mix of citrullinated and uncitrullinated.

Interestingly, no stimulus induced exclusively citrullinated or uncitrullinated NETs.

Further, PAD4 was required for citrullinated NETs only, whereas PAD2 was not required for either NET in mice.

Therefore, specific stimuli induce varying proportions of both citrullinated and uncitrullinated NETs with different requirements for PAD4.

These findings highlight the complexity of NET formation and the need to further define the mechanisms by which different NETs form and their implications for autoimmune disease.

American Psychological Association (APA)

Holmes, Caitlyn L.& Shim, Daeun& Kernien, John& Johnson, Chad J.& Nett, Jeniel E.& Shelef, Miriam A.. 2019. Insight into Neutrophil Extracellular Traps through Systematic Evaluation of Citrullination and Peptidylarginine Deiminases. Journal of Immunology Research،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1175823

Modern Language Association (MLA)

Holmes, Caitlyn L.…[et al.]. Insight into Neutrophil Extracellular Traps through Systematic Evaluation of Citrullination and Peptidylarginine Deiminases. Journal of Immunology Research No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1175823

American Medical Association (AMA)

Holmes, Caitlyn L.& Shim, Daeun& Kernien, John& Johnson, Chad J.& Nett, Jeniel E.& Shelef, Miriam A.. Insight into Neutrophil Extracellular Traps through Systematic Evaluation of Citrullination and Peptidylarginine Deiminases. Journal of Immunology Research. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1175823

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1175823