Participation of delta annexin A3 in the ribosomal protein S19 C‐terminus‐dependent inhibitory mechanism of the neutrophil C5a receptor through delta lactoferrin

Abstract

Although C5a receptor (C5aR) interacting with its agonist C5a promotes acute inflammation during the initiation phase, the roles of the recycling C5aR during the resolution phase are still unclear. We found that C5aR interacted with its antagonist/agonist ribosomal protein S19 (RP S19) polymer or a RP S19 polymer functional analogue S-tagged C5a/RP S19, which connects an RP S19 C-terminus (IAGQVAAANKKH) to the S-tagged C5a C-terminus, promoted acute inflammation at the resolution phase via an activation of the apoptosis-inducing transcription factor delta lactoferrin (δLf) in neutrophils and the membrane mobilizing factor full-length annexin A3 (ANXA3) in macrophages. To confirm the antagonistic system of the recycling C5aR, S-tagged δLf-coupled BrCN-activated Sepharose 4B beads were incubated with cytoplasmic proteins and identified a neutrophil-specific δANXA3 via pull-down experiments. The S-tagged C5a/RP S19-induced agonistic functions in macrophage-like cells that were differentiated from human promyelocytic leukemia HL-60 cells by phorbol-12-myristate-13-acetate were suppressed by δLf and δANXA3 co-overexpression. δANXA3 seems to participate in the antagonistic system of the neutrophil C5aR involving IAGQVAAANKKH and δLf. Most likely, δANXA3 works as antagonist for the recycling C5aR on neutrophils during the resolution phase of acute inflammation.

Elimination of Reference Mapping Bias Reveals Robust Immune Related Allele-Specific Expression in Crossbred Sheep

“…Fisher’s exact analysis at SNV level revealed ASE in response to LPS in variants within CLDN1 , ANXA3 , BRI3BP , SAA3 , and MSR1 ( Table 3 ). The anti-inflammatory macrophage marker CLDN1 (Van den Bossche et al, 2012) and acute-phase inflammation resolution marker ANXA3 (Yamanegi et al, 2018) have been previously reported with distinct macrophage functions. The macrophage scavenger receptor 1 ( MSR1 ) has also been shown to be involved in lipid uptake and migration ability of macrophages (Shi et al, 2019).…”

Integrated Bioinformatics Exploration and Preliminary Clinical Verification for the Identification of Crucial Biomarkers in Severe Cases of COVID-19

“…38 Considering the fact that ANXA3 expression is almost exclusive to neutrophils among circulating leucocytes, it may have potential effects on the host by facilitating neutrophil microbicidal function and pathogen clearance during sepsis. 39 ANXA3 could potentially contribute to inflammatory-induced lung damage in COVID-19 through the activation of nuclear factor-kappa B (NF-κB). This is because NF-κB plays a crucial role in inflammation and inhibiting the NF-κB pathway by upregulating IκBα has been observed with ANXA3 knockdown.…”