Lyn, one of the Src‐family tyrosine kinases expressed in phagocytes, plays an important role in <i>β</i>2 integrin‐signalling pathways in opsonized zymosan‐activated macrophage‐like U937 cells

Adachi, Reiko; Suzuki, Kazuhiro

doi:10.1002/cbf.1393

Cited by 11 publications

(6 citation statements)

References 61 publications

(56 reference statements)

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“…Phagocyte-derived reactive oxygen species (ROS) is of crucial importance for host resistance to bacterial infection [13]. Untreated AM cells and PMNs were isolated from mice to determine oxidative stress.…”

Section: Resultsmentioning

confidence: 99%

Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF‐κB pathway

Zhou

Yan

et al. 2013

Eur J Immunol

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Klebsiella pneumoniae is one of the most common pathogens in nosocomial infections and is becoming increasingly multidrug-resistant. However, the underlying molecular pathogenesis of this bacterium remains elusive, limiting the therapeutic options. Understanding the mechanism of its pathogenesis may facilitate the development of antibacterial therapeutics. Here, we show that Lyn, a pleiotropic Src tyrosine kinase, is involved in host defense against K. pneumoniae (Kp) by regulating phagocytosis process and simultaneously downregulating inflammatory responses. Using acute infection mouse models, we observed that lyn−/− mice were more susceptible to Kp with increased mortality and severe lung injury compared with wild-type mice. Kp infected-lyn−/− mice exhibited elevated inflammatory cytokines (IL-6 and TNF-α), and increased superoxide in the lung and other organs. In addition, the phosphorylation of p38 and NF-κB p65 subunit increased markedly in response to Kp infection in lyn−/− mice. We also demonstrated that the translocation of p65 from cytoplasm to nuclei increased in cultured murine lung epithelial cells by Lyn siRNA knockdown. Furthermore, lipid rafts clustered with activated Lyn and accumulated in the site of Kp invasion. Taken together, these findings revealed that Lyn may participate in host defense against Kp infection through the negative modulation of inflammatory cytokines.

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Section: Resultsmentioning

confidence: 99%

Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF‐κB pathway

Zhou

Yan

et al. 2013

Eur J Immunol

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“…Our data also demonstrate that the production of superoxides is dependent on Lyn. A recent study highlights the predominant role of Lyn in oxidative burst activity in opsonized zymosan-stimulated macrophages when compared with Hck and Fgr (62).…”

Section: Discussionmentioning

confidence: 99%

Cholesterol-Rich Membrane Rafts and Lyn Are Involved in Phagocytosis during Pseudomonas aeruginosa Infection

Kannan

Audet

Huang

et al. 2008

The Journal of Immunology

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The mechanism of phagocytosis of pathogens remains to be fully characterized. We report a novel phagocytosis pathway for Pseudomonas aeruginosa, which is initiated by cholesterol-rich membrane rafts and is dependent on Lyn, primarily an immune regulator with both positive and negative roles. Blocking of Lyn or blocking of cholesterol synthesis significantly inhibited phagocytosis by alveolar macrophages. We found that Lyn, via Src homology 2 and 3 domains, bound to and then activated PI3K and Akt to regulate intracellular routing of the engulfed P. aeruginosa. Further analysis indicates that Lyn and raft components entered in phagosomes and late lysosomes. Finally, respiratory burst was dependent on Lyn and membrane rafts, as confirmed by small interfering RNA and dominant-negative strategies. Our investigations demonstrate that Lyn along with membrane rafts plays a fundamental role in phagocytosis by alveolar macrophages during infection.

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“…In line with these findings, PGL-1 was then found to bind CR3 in vitro, through interaction of its sugar moiety with the lectin domain of the receptor (27). Moreover, Lyn, a Src-family tyrosine kinase mediating b2-integrin signaling in phagocytes (39), was recently involved in the PGL-1-dependent increase in macrophage invasion (27). Binding to CR3 and exploitation of CR3-mediated phagocytosis was unique to PGL-1, and was not observed with PGL from M. tuberculosis, M. bovis or M. ulcerans.…”

Section: Pgl and Cr3 Signalingmentioning

confidence: 54%

Pathogenic and immunosuppressive properties of mycobacterial phenolic glycolipids

Oldenburg

Demangel

2017

Biochimie

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Phenolic glycolipids (PGL) are polyketide synthase products that are uniquely produced by a subset of pathogenic mycobacteria and are displayed at the bacterial cell surface, in a strategic position to interfere with host immune cells. Their expression has been associated with enhanced mycobacterial virulence in vivo, and suppression of the inflammatory responses of host phagocytes in vitro. In this review, we will present our current understanding of the mode of operation of PGL, along with functional evidence that demonstrates the evolutionary advantage conferred by PGL production for host cell invasion, intracellular persistence and evasion of host immune and bactericidal responses.

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Lyn, one of the Src‐family tyrosine kinases expressed in phagocytes, plays an important role in β2 integrin‐signalling pathways in opsonized zymosan‐activated macrophage‐like U937 cells

Cited by 11 publications

References 61 publications

Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF‐κB pathway

Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF‐κB pathway

Cholesterol-Rich Membrane Rafts and Lyn Are Involved in Phagocytosis during Pseudomonas aeruginosa Infection

Pathogenic and immunosuppressive properties of mycobacterial phenolic glycolipids

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