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Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages.

ABSTRACT: Lactoferrin (LTF), an important first line defense molecule against infection, is a common target for humoral autoimmune reactions in humans. Since LTF is a multifunctional protein capable of activating innate immune cells via various surface receptors, we hypothesized that LTF-containing immune complexes (ICs) (LTF-ICs), likely formed in patients with high titer anti-LTF autoantibodies, could possess unique monocyte/macrophage-activating properties compared with other ICs. ELISA analysis on serum samples from rheumatoid arthritis (RA) patients (n?=?80) and healthy controls (n?=?35) for anti-LTF autoantibodies confirmed a positive correlation between circulating LTF-specific IgG and RA. ICs between human LTF and LTF-specific IgG purified from patient sera or immunized rabbits and mice, but not control ICs, LTF or Abs alone, elicited strong production of TNF-? and IL-1? by freshly fractionated human peripheral blood monocytes and monocytes-derived macrophages. Furthermore, LTF-ICs utilized both membrane-anchored CD14 and CD32a (Fc?RIIa) to trigger monocyte activation in an internalization-, Toll-like receptor (TLR)4- and TLR9-dependent manner, and also that LTF-IC-induced cytokine production was blocked by specific inhibitors of caspase-1, NF-?B and MAPK. These results uncover a possible pathway for LTF-ICs perpetuating local inflammation and contributing to the pathogenesis of autoimmune diseases by triggering activation of infiltrating monocytes or tissue macrophages in vivo.

SUBMITTER: Hu L

PROVIDER: S-EPMC5484712 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages.

Hu Lulu L Hu Xiaomin X Long Kai K Gao Chenhui C Dong Hong-Liang HL Zhong Qiao Q Gao Xiao-Ming XM Gong Fang-Yuan FY

Scientific reports 20170626 1

Lactoferrin (LTF), an important first line defense molecule against infection, is a common target for humoral autoimmune reactions in humans. Since LTF is a multifunctional protein capable of activating innate immune cells via various surface receptors, we hypothesized that LTF-containing immune complexes (ICs) (LTF-ICs), likely formed in patients with high titer anti-LTF autoantibodies, could possess unique monocyte/macrophage-activating properties compared with other ICs. ELISA analysis on ser ...[more]

PMID: 28652573

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Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages.

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Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages.

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