FcgammaR-induced production of superoxide and inflammatory cytokines is differentially regulated by SHIP through its influence on PI3K and/or Ras/Erk pathways
Authors: Julie Roda
William E Carson
Huiqing Fang
Periannan Kuppusamy
Rossana Trotta
John C Byrd
Susheela Tridandapani
Trupti Joshi
Latha P Ganesan
Amy Lehman
Michael A Caligiuri
Vijay Kumar Kutala
Journal: Blood (2006)
Discipline: CLINICAL MEDICINE
Keywords: Phagocytosis; FcgammaR; SHIP; superoxide; inflammatory cytokines
Affiliations: Department of Internal Medicine, The Ohio State University Biochemistry Program, Columbus, USA., From the Department of Internal Medicine and Comprehensive Cancer Center; The Ohio State University Biochemistry Program; Department of Molecular Virology, Immunology, and Medical Genetics; and Biostatistics Program, The Ohio State University, Columbus.

Abstract:  Phagocytosis of IgG-coated particles via FcgammaR is accompanied by the generation of superoxide and inflammatory cytokines, which can cause collateral tissue damage in the absence of regulation. Molecular mechanisms regulating these phagocytosis-associated events are not known. SHIP is an inositol phosphatase that downregulates PI3K-mediated activation events. Here, we have examined the role of SHIP in FcgammaR-induced production of superoxide and inflammatory cytokines. We report that primary SHIP-deficient bone marrow macrophages produce elevated levels of superoxide upon FcgammaR clustering. Analysis of the molecular mechanism revealed that SHIP regulates upstream Rac-GTP binding, an obligatory event for superoxide production. Likewise, SHIP-deficient macrophages displayed enhanced IL-1beta and IL-6 production in response to FcgammaR clustering. Interestingly, whereas IL-6 production required activation of both PI3K and Ras/Erk pathways, IL-1beta production was dependent only on Ras/Erk activation, suggesting that SHIP may also regulate the Ras/Erk pathway in macrophages. Consistently, SHIP-deficient macrophages displayed enhanced activation of Erk upon FcgammaR clustering. Inhibition of Ras/Erk or PI3K suppressed the enhanced production of IL-6 in SHIP-deficient macrophages. In contrast, inhibition of Ras/Erk, but not PI3K, suppressed IL-1beta production in these cells. Together, these data demonstrate that SHIP regulates phagocytosis-associated events through the inhibition of PI3K and Ras/Erk pathways. 

Retracted: No

PubPeer comments:
 In Section IV, Part-C of the above paper, the authors provide an improvement of the so-called MCC algorithm. This improvement seems to be one of the salient contributions of this paper. However, the following paper also provides a similar algorithm. Title: **Fingerprint Access Control for Wireless Insulin Pump Systems Using Cancelable Delaunay Triangulations** authored by *G.Zheng, W.Yang, C.Valli, R,Shankaran, H.Abbas, G.Zhang, G.Fang, J.Chaudhry* and *L.Qiao* and Published in **IEEE Access** (Available online Jun 2019). In the introduction, the Jun 2019 paper cites the July 2019 paper (with the bibliography stating that the July 2019 paper is yet to be published). Very likely, the reviewers editors of the Jun 2019 paper did not have access to the July 2019 paper. In fact, in the introduction, the Jun 2019 paper says **...It is quite challenging to distribute the key to the very hospital or clinic in a timely manner and manage the key securely thereafter [9]....** where [9] is the above July 2019 paper titled **Finger-to-Heart (F2H): Authentication for Wireless Implantable Medical Devices** However, neither paper cites the other in the context of the new contributions (improvement to the MCC algorithm). Thus, the improvement of the so-called MCC algorithm looks new in both the papers. ,