Absence of Fer protein tyrosine kinase exacerbates endotoxin induced intestinal epithelial barrier dysfunction in vivo

Qi, Weier; Ebbert, Kirsten; Craig, Andrew W.B.; Greer, Peter A.; McCafferty, Donna–Marie

doi:10.1136/gut.2004.061887

Cited by 27 publications

(24 citation statements)

References 43 publications

(43 reference statements)

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“…an acute immune response in insects (23). Similar observations are reported in mammals at early stages of infection (24). In contrast, when silkworms were injected with a live suspension of S. marcescens, the decrease in the free hemocyte number was suppressed (Fig.…”

Section: Decrease In Silkworm Hemocyte Number By Injury Stimulation Asupporting

confidence: 71%

Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells

Ishii

Adachi

Hamamoto

et al. 2014

Journal of Biological Chemistry

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Section: Decrease In Silkworm Hemocyte Number By Injury Stimulation Asupporting

confidence: 71%

Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells

Ishii

Adachi

Hamamoto

et al. 2014

Journal of Biological Chemistry

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“…Surprisingly, FcεRI-induced tyrosine phosphorylation of Fes and Fer does not require their kinase activities (55) and is almost entirely dependent on Lyn (67). Through the use of transgenic mouse models, evidence for both unique and redundant functions for Fes and Fer has been described in regulating hematopoiesis (55) and limiting the innate immune response (22,40,50,72). In mast cells, we have shown that Fer promotes activation of p38 mitogen-activated protein kinase and chemotaxis of mast cells (10).…”

mentioning

confidence: 92%

Contributions of F-BAR and SH2 Domains of Fes Protein Tyrosine Kinase for Coupling to the FcεRI Pathway in Mast Cells

McPherson

Everingham

Karisch

et al. 2009

Molecular and Cellular Biology

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“…Although these mice are viable and overtly normal, we have dem-onstrated enhanced leukocyte recruitment in response to LPS challenge in vivo (20,21). These studies suggest that Fer plays a role in limiting leukocyte recruitment across endothelial and epithelial barriers in response to bacterial Ag.…”

mentioning

confidence: 75%

“…Previously, we have demonstrated a role for the group IV nonreceptor PTKs, Fer (20,21) and Fes (30,31), in leukocyte recruitment in vivo in response to local LPS injection. LPS induces recruitment through the induction of many different chemoattractants.…”

Section: Discussionmentioning

confidence: 97%

“…Our previous studies have implicated Fer in limiting leukocyte recruitment in response to LPS challenge in cremaster muscle and the gut epithelium (20,21). In the latter study, mice devoid of Fer kinase activity (Fer DR/DR ) displayed defects that were partly attributable to altered neutrophil function.…”

Section: Absence Of Fer Kinase Does Not Alter Basal Intravascular Leumentioning

confidence: 94%

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Fer Kinase Limits Neutrophil Chemotaxis toward End Target Chemoattractants

Khajah

Andonegui

Chan

et al. 2013

The Journal of Immunology

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Neutrophil recruitment and directional movement toward chemotactic stimuli are important processes in innate immune responses. This study examines the role of Fer kinase in neutrophil recruitment and chemotaxis to various chemoattractants in vitro and in vivo. Mice targeted with a kinase-inactivating mutation (FerDR/DR) or wild type (WT) were studied using time-lapse intravital microscopy to examine leukocyte recruitment and chemotaxis in vivo. In response to keratinocyte-derived cytokine, no difference in leukocyte chemotaxis was observed between WT and FerDR/DR mice. However, in response to the chemotactic peptide WKYMVm, a selective agonist of the formyl peptide receptor, a 2-fold increase in leukocyte emigration was noted in FerDR/DR mice (p < 0.05). To determine whether these defects were due to Fer signaling in the endothelium or other nonhematopoietic cells, bone marrow chimeras were generated. WKYMVm-induced leukocyte recruitment in chimeric mice (WT bone marrow to FerDR/DR recipients or vice versa) was similar to WT mice, suggesting that Fer kinase signaling in both leukocytes and endothelial cells serves to limit chemotaxis. Purified FerDR/DR neutrophils demonstrated enhanced chemotaxis toward end target chemoattractants (WKYMVm and C5a) compared with WT using an under-agarose gel chemotaxis assay. These defects were not observed in response to intermediate chemoattractants (keratinocyte-derived cytokine, MIP-2, or LTB4). Increased WKYMVm-induced chemotaxis of FerDR/DR neutrophils correlated with sustained PI3K activity and reduced reliance on the p38 MAPK pathway compared with WT neutrophils. Together, these data identify Fer as a novel inhibitory kinase for neutrophil chemotaxis toward end target chemoattractants through modulation of PI3K activity.

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Absence of Fer protein tyrosine kinase exacerbates endotoxin induced intestinal epithelial barrier dysfunction in vivo

Cited by 27 publications

References 43 publications

Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells

Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells

Contributions of F-BAR and SH2 Domains of Fes Protein Tyrosine Kinase for Coupling to the FcεRI Pathway in Mast Cells

Fer Kinase Limits Neutrophil Chemotaxis toward End Target Chemoattractants

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