EXPRESSION OF ARGINASE 1 (ARG1), THE ALTERNATIVE ACTIVATED MACROPHAGES MARKER IN RAT MODEL OF CARDIAC TRANSPLANTATION

2008 ◽  
Vol 86 (Supplement) ◽  
pp. 506
Author(s):  
Y Chen ◽  
Y Liu ◽  
Z Yuan ◽  
J Lamb ◽  
P K.H. Tam
Keyword(s):  
Rat Model ◽  
Cardiac Transplantation ◽  
Activated Macrophages ◽  
Arginase 1

scholarly journals Arginase in Parasitic Infections: Macrophage Activation, Immunosuppression, and Intracellular Signals

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Cinthia C. Stempin ◽  
Laura R. Dulgerian ◽  
Vanina V. Garrido ◽  
Fabio M. Cerban
Keyword(s):  
Macrophage Activation ◽  
Transforming Growth Factor ◽  
Parasite Clearance ◽  
Alternative Activation ◽  
Parasitic Infections ◽  
Activated Macrophages ◽  
Proinflammatory Response ◽  
Alternatively Activated Macrophages ◽  
Arginase 1

A type 1 cytokine-dependent proinflammatory response inducing classically activated macrophages (CaMϕs) is crucial for parasite control during protozoan infections but can also contribute to the development of immunopathological disease symptoms. Type 2 cytokines such as IL-4 and IL-13 antagonize CaMϕs inducing alternatively activated macrophages (AaMϕs) that upregulate arginase-1 expression. During several infections, induction of arginase-1-macrophages was showed to have a detrimental role by limiting CaMϕ-dependent parasite clearance and promoting parasite proliferation. Additionally, the role of arginase-1 in T cell suppression has been explored recently. Arginase-1 can also be induced by IL-10 and transforming growth factor-β(TGF-β) or even directly by parasites or parasite components. Therefore, generation of alternative activation states of macrophages could limit collateral tissue damage because of excessive type 1 inflammation. However, they affect disease outcome by promoting parasite survival and proliferation. Thus, modulation of macrophage activation may be instrumental in allowing parasite persistence and long-term host survival.

scholarly journals LATE BLOCKADE OF B7-1 COSTIMULATION INTERRUPTS THE DEVELOPMENT OF CHRONIC REJECTION IN A RAT MODEL OF CARDIAC TRANSPLANTATION

1998 ◽  
Vol 65 (12) ◽  
pp. S182
Author(s):  
M D. Denton ◽  
A. Knoflach ◽  
R. Milord ◽  
A. Chandraker ◽  
L. A. Turka ◽  
...  
Keyword(s):  
Rat Model ◽  
Chronic Rejection ◽  
Cardiac Transplantation

Alternatively activated macrophages engage in homotypic and heterotypic interactions through IL-4 and polyamine-induced E-cadherin/catenin complexes

Blood ◽  
2009 ◽  
Vol 114 (21) ◽  
pp. 4664-4674 ◽  
Author(s):  
Jan Van den Bossche ◽  
Pieter Bogaert ◽  
Jolanda van Hengel ◽  
Christopher J. Guérin ◽  
Geert Berx ◽  
...  
Keyword(s):  
Allergic Airway Inflammation ◽  
Interleukin 4 ◽  
Cell Contact ◽  
Cellular Interactions ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Arginase 1 ◽  
Heterotypic Interactions ◽  
Alternatively Activated ◽  
E Cadherin

Abstract Alternatively activated macrophages (AAMs), triggered by interleukin-4 (IL-4) and IL-13, play a modulating role during Th2 cytokine-driven pathologies, but their molecular armament remains poorly characterized. Here, we established E-cadherin (Cdh1) as a selective marker for IL-4/IL-13–exposed mouse and human macrophages, which is STAT6-dependently induced during polarized Th2 responses associated with Taenia crassiceps helminth infections or allergic airway inflammation. The IL-4–dependent, arginase-1/ornithine decarboxylase–mediated production of polyamines is important for maximal Cdh1 induction, unveiling a novel mechanism for IL-4–dependent gene transcription. At the macrophage surface, E-cadherin forms a functional complex with the catenins that accumulates at sites of cell contact. Macrophage-specific deletion of the Cdh1 gene illustrates the implication of E-cadherin in IL-4–driven macrophage fusion and heterotypic interactions with CD103+ and KLRG1+ T cells. This study identifies the E-cadherin/catenin complex as a discriminative, partly polyamine-regulated feature of IL-4/IL-13–exposed alternatively activated macrophages that contributes to homotypic and heterotypic cellular interactions.

scholarly journals Extraintestinal Helminth Infection Limits Pathology and Proinflammatory Cytokine Expression during DSS-Induced Ulcerative Colitis: A Role for Alternatively Activated Macrophages and Prostaglandins

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Yadira Ledesma-Soto ◽  
Blanca E. Callejas ◽  
César A. Terrazas ◽  
Jose L. Reyes ◽  
Arlett Espinoza-Jiménez ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Activity Index ◽  
Disease Activity Index ◽  
Helminth Parasites ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Arginase 1 ◽  
Alternatively Activated

Chronic inflammation of the intestinal mucosa is characteristic of inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease. Helminth parasites have developed immunomodulatory strategies that may impact the outcome of several inflammatory diseases. Therefore, we investigated whetherTaenia crassicepsinfection is able to decrease the inflammatory effects of dextran sulfate sodium- (DSS-) induced ulcerative colitis in BALB/c and C57BL/6 mice. Preinfection significantly reduced the manifestations of DSS-induced colitis, as weight loss and shortened colon length, and decreased the disease activity index independently of the genetic background of the mice.Taeniainfection decreased systemic levels of proinflammatory cytokines while increasing levels of IL-4 and IL-10, and the inflammatory infiltrate into the colon was also markedly reduced. RT-PCR assays from colon showed thatT. crassiceps-infected mice displayed increased expression of Arginase-1 but decreased expression of iNOS compared to DSS-treated uninfected mice. The percentages of T regulatory cells were not increased. The adoptive transfer of alternatively activated macrophages (AAMФs) from infected mice into mice with DSS-induced colitis reduced the severity of colon inflammation. Administration of indomethacin abrogated the anticolitic effect ofTaenia. Thus,T. crassicepsinfection limits the pathology of ulcerative colitis by suppressing inflammatory responses mechanistically associated with AAMФs and prostaglandins.

scholarly journals The effects of the M2a macrophage-induced axonal regeneration of neurons by arginase 1

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Jieyuan Zhang ◽  
Yue Li ◽  
Zhaoxia Duan ◽  
Jianyi Kang ◽  
Kuijun Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Rat Model ◽  
Axonal Regeneration ◽  
Local Area ◽  
Type I ◽  
Specific Mechanism ◽  
Neuronal Marker ◽  
Raw264.7 Macrophages ◽  
Arginase 1 ◽  
Cord Injury

Abstract Background: Spinal cord injury (SCI) is a challenge worldwide, but there are no effective treatments or therapeutic methods in the clinic. Recent studies have shown that type I arginase (Arginase1, Arg1) is closely associated with the treatment of SCI. The classical treatment for SCI involves filling the local area of SCI with activated M2a macrophages to allow the repair and regeneration of some synapses, but the specific mechanism of action of Arg1 is not clear. Method: In the present study, we first induced the polarization of RAW264.7 macrophages to M2a-type cells using IL-4 and constructed an Arg1 knockout cell line through the use of shRNA; we used these cells to treat a rat model of SCI. Finally, the present study explored the mechanism and pathway by which Arginase 1 regulates spinal repair by immunoblotting and immunohistochemistry. Result: Suspended M2a (Arg1-/+) macrophages were transplanted into the injury site in a rat model of contusion SCI. Compared with the model group and the shArg1 group, the shScramble (shSc) group exhibited higher Basso, Beattie, Bresnahan motor function scores, more compact structures and more Nissl bodies. Immunohistochemical results showed that the shSc group expressed higher levels of NeuN (a neuronal marker) and tau (an axonal marker), as well as the up-regulation of Cdc42, N-WASP, Arp2/3 and tau, as determined by Western blot. Conclusion: The study found that the polarization of M2a macrophages promoted the expression of Arginase 1, which restored axonal regeneration, promoted axonal regeneration, and promoted the structural and functional recovery of the contused spinal cord.

scholarly journals Utilization of Host Polyamines in Alternatively Activated Macrophages Promotes Chronic Infection byBrucella abortus

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Tobias Kerrinnes ◽  
Maria G. Winter ◽  
Briana M. Young ◽  
Vladimir E. Diaz-Ochoa ◽  
Sebastian E. Winter ◽  
...  
Keyword(s):  
Chronic Infection ◽  
Intracellular Survival ◽  
Interleukin 4 ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Content Type ◽  
Arginase 1 ◽  
Long Course ◽  
Multiple Drugs ◽  
Alternatively Activated

ABSTRACTTreatment of intracellular bacterial pathogens with antibiotic therapy often requires a long course of multiple drugs. A barrier to developing strategies that enhance antibiotic efficacy against these pathogens is our poor understanding of the intracellular nutritional environment that maintains bacterial persistence. The intracellular pathogenBrucella abortussurvives and replicates preferentially in alternatively activated macrophages (AAMs); however, knowledge of the metabolic adaptations promoting exploitation of this niche is limited. Here we show that one mechanism promoting enhanced survival in AAMs is a shift in macrophage arginine utilization from production of nitric oxide (NO) to biosynthesis of polyamines, induced by interleukin 4 (IL-4)/IL-13 treatment. Production of polyamines by infected AAMs promoted both intracellular survival ofB. abortusand chronic infection in mice, as inhibition of macrophage polyamine synthesis or inactivation of the putative putrescine transporter encoded bypotIHGFreduced both intracellular survival in AAMs and persistence in mice. These results demonstrate that increased intracellular availability of polyamines induced by arginase-1 expression in IL-4/IL-13-induced AAMs promotes chronic persistence ofB. abortuswithin this niche and suggest that targeting of this pathway may aid in eradicating chronic infection.

scholarly journals High Content Image Analysis as a Tool to Morphologically Distinguish Macrophage Activation and Determine Its Importance for Foamy Alveolar Macrophage Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Ewelina Hoffman ◽  
Paulina Napieralska ◽  
Rhamiya Mahendran ◽  
Darragh Murnane ◽  
Victoria Hutter
Keyword(s):  
Image Analysis ◽  
Alveolar Macrophage ◽  
Safety Assessment ◽  
Macrophage Activation ◽  
Activated Macrophages ◽  
Analysis Techniques ◽  
Arginase 1 ◽  
Ifn Γ ◽  
Macrophage Phenotypes ◽  
Image Analysis Techniques

IntroductionLung diseases are an increasing global health burden affecting millions of people worldwide. Only a few new inhaled medicines have reached the market in the last 30 years, in part due to foamy alveolar macrophage (FAM) responses observed in pre-clinical rat studies. The induction mechanism and signaling pathways involved in the development of highly vacuolated ‘foamy’ phenotype is not known. Furthermore, it has not been determined if these observations are adaptive or adverse responses.AimTo determine if high content image analysis techniques can distinguish between alveolar macrophage activation (LPS/IFN-γ activated and IL-4 activated macrophages) and if this could be applied to understanding the generation of ‘foamy’ macrophage phenotypes.MethodsNR8383 rat alveolar macrophages were stimulated with a mix of cytokines (LPS/IFN-γ or IL-4) for 24 h. The cells were further exposed to FAM inducing-compounds amiodarone and staurosporine. Following 24 h incubation, phagocytosis and lipid accumulation were measured using flow cytometry and high content image analysis techniques. The alveolar macrophages responses after exposure to cytokines were assessed by evaluation: (i) cell surface and biochemical markers such as: nitric oxide production, arginase-1 activity and MRC-1 receptor expression (ii) cellular morphology (iii) cellular functionality (phagocytic activity and lipids accumulation).ResultsMacrophages activated with LPS/IFN-γ showed distinct morphological (increased vacuolation) features and functionality (increased lipidosis, decreased phagocytic activity). Foamy macrophage phenotypes induced by amiodarone also displayed characteristics of proinflammatory macrophages (significantly increased nitric oxide production, increased vacuolation and lipidosis and decreased phagocytosis). In contrast, staurosporine treatment resulted in increased NO production, as well as arginase-1 activity.ConclusionHigh content image analysis was able to determine distinct differences in morphology between non-activated and LPS/IFN-γ activated macrophages, characterized by increased vacuolation and lipidosis. When exposed to compounds that induce a FAM phenotype, healthy non-activated macrophages displayed proinflammatory (amiodarone) or pro-apoptotic (staurosporine) characteristics but these responses were independent of a change in activation status. This technique could be applied in early drug discovery safety assessment to identify immune responses earlier and increase the understanding of alveolar macrophage responses to new molecules challenge in development of new inhalation therapies, which in turn will enhance decision-making in an early safety assessment of novel drug candidates.

scholarly journals SIRPα sequesters SHP-2 to promote IL-4/13 signaling and alternative activation of macrophages

2021 ◽  
Author(s):  
Lei Shi ◽  
Koby Kidder ◽  
Zhen Bian ◽  
Samantha Kuon Ting Chiang ◽  
Corbett Ouellette ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Experimental Colitis ◽  
Alternative Activation ◽  
Activated Macrophages ◽  
Negative Regulators ◽  
Impaired Wound Healing ◽  
Alternatively Activated Macrophages ◽  
Arginase 1 ◽  
Alternatively Activated

The Th2 cytokines IL-4 and IL-13 through activation of their shared receptor IL-4Rα direct macrophage alternative activation to promote immunosuppression and wound healing. However, the mechanisms that control macrophage responses to IL-4/13 are not fully understood. Apart from driving JAK-STAT and PI3K-Akt pathways to polarize macrophages toward the alternative phenotype, the activated IL-4/13 receptors recruit negative regulators SHP-1 and SHP-2, which dephosphorylate IL-4Rα and decrease its signaling. Here we report that SIRPα spatially restricts SHP-2 and, by such, promotes IL-4/13 signaling and macrophage alternative activation. SIRPα executes this regulation via its cytoplasmic ITIMs/ITSMs that undergo phosphorylation by IL-4/13-induced, Src kinase-activated Brutons tyrosine kinase (Btk), resulting in recruitment of SHP-2 and preclusion of SHP-2 from binding to and inhibiting IL-4/13 receptors. Despite that this regulation occurs independent of CD47, extracellular CD47 ligation of SIRPα facilitates its cytoplasmic phosphorylation and SHP-2 sequestration, leading to stronger IL-4/13 signaling and enhanced macrophage expression of IL-10, TGFβ, CD206, arginase-1, etc. Conversely, deficiency of SIRPα allows SHP-2 to freely bind to γC or IL-13Rα1 and through which dephosphorylate IL-4Rα, dampening its signaling. Consistent with these findings, impaired wound healing in Sirpα-/- mice under experimental colitis correlated with a deficit of immunosuppressive macrophages in the colon, a condition that was corrected by transfusion of ex vivo-produced SIRPαhigh alternatively activated macrophages.

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