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Hum Immunol. 2016 Dec;77(12):1209-1214. doi: 10.1016/j.humimm.2016.08.006. Epub 2016 Aug 18.

Macrophage migration inhibitory factor contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation.

Author information

1
Renal Division, Department of Medicine, The Affiliated Hospital of Inner Mongolia Medical College, Huhehot, Inner Mongolia 010050, China. Electronic address: Jian_hao8865@126.com.
2
Renal Division, Department of Medicine, The Affiliated Hospital of Inner Mongolia Medical College, Huhehot, Inner Mongolia 010050, China.
3
Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China.
4
Department of Pharmacology, Inner Mongolia Medical College, Huhehot, Inner Mongolia 010010, China.

Abstract

BACKGROUND:

Macrophage migration inhibitory factor (MIF) is an inflammatory mediator released by macrophages that is central to the innate immune system, with an upstream role in the inflammatory cascade. MIF is one of the most important pathogenic factors in the development of the autoimmune diseases. In the current study, we investigated the role of MIF in anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation.

METHODS:

Plasma levels of MIF from 31 patients with active ANCA-associated vasculitis (AAV) were analyzed by ELISA. The various effects of MIF in ANCA-induced neutrophil respiratory burst and degranulation were measured.

RESULTS:

Plasma levels of circulating MIF were significantly higher in AAV patients with active disease compared with those in remission and healthy controls. Compared with MIF-primed neutrophils, the MFI value increased significantly in MIF-primed neutrophils further activated with MPO-ANCA-positive IgG or PR3-ANCA-positive IgG (270.8±9.7 vs. 421.5±9.7, P<0.001; 270.8±9.7 vs. 414.1±15.6, P<0.001, respectively). Compared with MIF-primed neutrophils, the lactoferrin concentration increased significantly in the supernatant of MIF-primed neutrophils further activated by MPO-ANCA-positive IgG (567.8±61.2ng/ml vs. 1677.0±42.5ng/ml, P<0.001) or PR3-ANCA-positive IgG (567.8±61.2ng/ml vs. 1546.0±116.2ng/ml, P<0.001), respectively. Interleukin-8 (IL-8), IL-6 and IL-23 were involved in ANCA-induced activation of MIF-primed neutrophils.

CONCLUSIONS:

MIF primes neutrophils by increasing ANCA antigen translocation. The primed neutrophils can be further induced by ANCA, resulting in respiratory burst and degranulation.

KEYWORDS:

ANCA; Macrophage migration inhibitory factor; Neutrophils

PMID:
27544048
DOI:
10.1016/j.humimm.2016.08.006
[Indexed for MEDLINE]

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