scholarly journals Human macrophage activation. Modulation of mannosyl, fucosyl receptor activity in vitro by lymphokines, gamma and alpha interferons, and dexamethasone.

1985 ◽  
Vol 75 (2) ◽  
pp. 624-631 ◽  
Author(s):  
T Mokoena ◽  
S Gordon
Keyword(s):  
Macrophage Activation ◽  
Receptor Activity ◽  
Human Macrophage

Abstract 649: PARP14 and PARP9 Are Novel Regulators of Macrophage Activation

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Hiroshi Iwata ◽  
Piero Ricchiuto ◽  
Takuya Hara ◽  
Amitabh Sharma ◽  
Alex Mojcher ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Macrophage Polarization ◽  
Vascular Diseases ◽  
Interleukin 4 ◽  
Human Macrophage ◽  
Physical Interaction ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Purpose: A microenvironment dominant in pro-inflammatory macrophages (“M1”) and lacking anti-inflammatory macrophages (“M2”) may promote vascular diseases. We explored and validated key regulators of such macrophage polarization. Methods and Results: Using global proteomic analysis and bioinformatics, we examined the changes in the proteomes of mouse and human macrophage cell lines (RAW264.7; THP-1) in response to interferon gamma (IFNγ) or interleukin 4 (IL-4) for M1 or M2 polarization, respectively. Among 5816 proteins in RAW264.7 and 4723 in THP-1, data filtering and clustering identified poly(ADP-ribose) polymerase 14 (PARP14) and 9 (PARP9) as candidates for key regulators of macrophage polarization, which increase in M1 and decrease in M2 condition. siRNA silencing of PARP14 in macrophages induced M1 genes TNF-α, IL-1β and iNOS, while decreased M2 markers Arg1 and MRC1, indicating that PARP14 suppresses pro-inflammatory macrophage activation and promotes anti-inflammatory polarization. PARP14 silencing induced STAT1 phosphorylation and reduced STAT6 phosphorylation, suggesting their roles in the underlying signaling mechanisms. In contrast, PARP9 silencing decreased M1 markers, as well as phosphorylation of STAT1. Of interest, a direct physical interaction between PARP14 and PARP9 was also demonstrated. In vivo evidence supported these in vitro findings. Macrophages of PARP14-deficient mice expressed markedly higher levels of M1 genes and lower levels M2 markers. PARP14 deficiency accelerated lesion development after mechanical injury in femoral arteries. Conclusions: PARP14 and PARP9 regulate macrophage activation, offering novel therapeutic targets for vascular diseases.

scholarly journals Low Intensity Shockwave Treatment Modulates Macrophage Functions Beneficial to Healing Chronic Wounds

2021 ◽  
Vol 22 (15) ◽  
pp. 7844
Author(s):  
Jason S. Holsapple ◽  
Ben Cooper ◽  
Susan H. Berry ◽  
Aleksandra Staniszewska ◽  
Bruce M. Dickson ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Immunohistochemical Analysis ◽  
Therapeutic Effects ◽  
Gene Expressions ◽  
Extracorporeal Shock Wave

Extracorporeal Shock Wave Therapy (ESWT) is used clinically in various disorders including chronic wounds for its pro-angiogenic, proliferative, and anti-inflammatory effects. However, the underlying cellular and molecular mechanisms driving therapeutic effects are not well characterized. Macrophages play a key role in all aspects of healing and their dysfunction results in failure to resolve chronic wounds. We investigated the role of ESWT on macrophage activity in chronic wound punch biopsies from patients with non-healing venous ulcers prior to, and two weeks post-ESWT, and in macrophage cultures treated with clinical shockwave intensities (150–500 impulses, 5 Hz, 0.1 mJ/mm2). Using wound area measurements and histological/immunohistochemical analysis of wound biopsies, we show ESWT enhanced healing of chronic ulcers associated with improved wound angiogenesis (CD31 staining), significantly decreased CD68-positive macrophages per biopsy area and generally increased macrophage activation. Shockwave treatment of macrophages in culture significantly boosted uptake of apoptotic cells, healing-associated cytokine and growth factor gene expressions and modulated macrophage morphology suggestive of macrophage activation, all of which contribute to wound resolution. Macrophage ERK activity was enhanced, suggesting one mechanotransduction pathway driving events. Collectively, these in vitro and in vivo findings reveal shockwaves as important regulators of macrophage functions linked with wound healing. This immunomodulation represents an underappreciated role of clinically applied shockwaves, which could be exploited for other macrophage-mediated disorders.

scholarly journals Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation.

1980 ◽  
Vol 152 (6) ◽  
pp. 1596-1609 ◽  
Author(s):  
H W Murray ◽  
Z A Cohn
Keyword(s):  
Antimicrobial Activity ◽  
Oxidative Metabolism ◽  
Macrophage Activation ◽  
Systemic Infection ◽  
Peritoneal Macrophages ◽  
H2o2 Production ◽  
Oxygen Intermediates ◽  
Cultivation In Vitro

The capacity of 15 separate populations of mouse peritoneal macrophages to generate and release H2O2 (an index of oxidative metabolism) was compared with their ability to inhibit the intracellular replication of virulent Toxoplasma gondii. Resident macrophages and those elicited by inflammatory agents readily supported toxoplasma multiplication and released 4-20X less H2O2 than macrophages activated in vivo by systemic infection with Bacille Calmette-Guérin or T. gondii, or by immunization with Corynebacterium parvum. Immunologically activated cells consistently displayed both enhanced H2O2 production and antitoxoplasma activity. Exposure to lymphokines generated from cultures of spleen cells from T. gondii immune mice and toxoplasma antigen preserved both the antitoxoplasma activity and the heightened H2O2 release of toxoplasma immune and immune-boosted macrophages, which otherwise were lost after 48-72 h of cultivation. In vitro activation of resident and chemically-elicited cells by 72 h of exposure to mitogen- and antigen-prepared lymphokines, conditions that induce trypanocidal (5) and leishmanicidal activity (14), stimulated O2- and H2O2 release, and enhanced nitroblue tetrazolium reduction in response to toxoplasma ingestion. Such treatment, however, failed to confer any antitoxoplasma activity, indicating that intracellular pathogens may vary in their susceptibility to macrophage microbicidal mechanisms, including specific oxygen intermediates. In contrast, cocultivating normal macrophages with lymphokine plus heart infusion broth for 18H rendered these cells toxoplasmastatic. This in vitro-acquired activity was inhibited by scavengers of O2-, H2O2, OH., and 1O2, demonstrating a role for oxidative metabolites in lymphokine-induced enhancement of macrophage antimicrobial activity. These findings indicate that augmented oxidative metabolism is an consistent marker of macrophage activation, and that oxygen intermediates participate in the resistance of both in vivo- and vitro-activated macrophages toward the intracellular parasite, T. gondii.

Macrophages in dermal disease progression of phospholipase D4–deficient Fleckvieh calves

2021 ◽  
pp. 030098582110626
Author(s):  
Martin C. Langenmayer ◽  
Simone Jung ◽  
Robert Fux ◽  
Christina Wittlinger ◽  
Theresa Tschoner ◽  
...  
Keyword(s):  
Disease Progression ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Quantitative Polymerase Chain Reaction ◽  
Skin Lesions ◽  
Human Macrophage ◽  
Gene Encoding ◽  
Pathway Activation ◽  
Microbial Dna ◽  
Activation Syndrome

A new gene defect in Fleckvieh calves leads to a syndrome with partial phenotype overlap with bovine hereditary zinc deficiency. A mutation in a gene encoding phospholipase D4 ( PLD4), an endosomal exonuclease, causes the disorder. In mice, PLD4 activity indirectly regulates the Toll-like receptor 9 (TLR9) pathway via degradation of microbial DNA. PLD4 absence thus results in visceral macrophage activation comparable to human macrophage activation syndrome. In this study, disease progression and the role of macrophages in affected calves were monitored clinically, clinicopathologically, and histologically over time. Breeding data identified 73 risk matings of heterozygous carriers resulting in 54 potentially PLD4-deficient calves born on farms. PLD4 status was examined via 5′-exonuclease assay, detecting 6 calves carrying the defect. These were purchased and monitored daily until final necropsy. The calves developed progressive skin lesions starting with small scaling areas terminating in severe crusting dermatitis, especially in areas with mechanical exposure. Histological and immunohistochemical analyses indicated that macrophages with cytoplasmic vacuolation increased considerably in skin sections obtained weekly during the disease course. Macrophage increase correlated with increased dermal lesion severity. Macrophage activation was confirmed by prominent phagocytic activity in the superficial dermis using electron microscopy. Dermal mRNA abundance of CCL2 and CCL3 measured by quantitative polymerase chain reaction verified macrophage activation. Further increase in mRNA of downstream molecule MyD88 and cytokine IL12b connected bovine PLD4 deficiency to increased TLR9 pathway activation. In contrast to human macrophage activation syndrome, the main feature of bovine PLD4 deficiency was local disease in organs with contact to microbial DNA (skin, intestine, lungs).

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