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Tissue-resident alveolar macrophages (TR-AM) are depleted from the lung during the early stages of bleomycin-induced lung injury and fibrosis. The recovery of the population of macrophages after bleomycin could be completely attributable to the recruitment and differentiation of monocyte-derived alveolar macrophages (Mo-AM). The authors used multiple lineage-trace mouse models where they selectively depleted TR-AM or Mo-AM and induced fibrosis with bleomycin. Deletion of TR-AM had no effect on the severity of the fibrotic phenotype...
December 2017: Breathe
Jonathan M Weiss, Luke C Davies, Megan Karwan, Lilia Ileva, Michelle K Ozaki, Robert Ys Cheng, Lisa A Ridnour, Christina M Annunziata, David A Wink, Daniel W McVicar
Control of cellular metabolism is critical for efficient cell function, although little is known about the interplay between cell subset-specific metabolites in situ, especially in the tumor setting. Here, we determine how a macrophage-specific metabolite, itaconic acid, can regulate tumor progression in the peritoneum. We show peritoneal tumors (B16 melanoma or ID8 ovarian carcinoma) elicited a fatty acid oxidation-mediated increase in oxidative phosphorylation (OXPHOS) and glycolysis in peritoneal tissue-resident macrophages (pResMφ)...
June 19, 2018: Journal of Clinical Investigation
Yoko Okunuki, Ryo Mukai, Elizabeth A Pearsall, Garrett Klokman, Deeba Husain, Dong-Ho Park, Ekaterina Korobkina, Howard L Weiner, Oleg Butovsky, Bruce R Ksander, Joan W Miller, Kip M Connor
Retinal detachment (RD) is a sight-threatening complication common in many highly prevalent retinal disorders. RD rapidly leads to photoreceptor cell death beginning within 12 h following detachment. In patients with sustained RD, progressive visual decline due to photoreceptor cell death is common, leading to significant and permanent loss of vision. Microglia are the resident immune cells of the central nervous system, including the retina, and function in the homeostatic maintenance of the neuro-retinal microenvironment...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Brian E Cairns, Lars Arendt-Nielsen, Paola Sacerdote
Background It is unknown why an acute pain condition under various circumstances can transition into a chronic pain condition. There has been a shift towards neuroinflammation and hence glial cell activations specifically in the dorsal root ganglion and spinal cord as a mechanism possibly driving the transition to chronic pain. This has led to a focus on non-neuronal cells in the peripheral and central nervous system. Besides infiltrating macrophages, Schwann cells and satellite glial cells release cytokines and therefore important mechanisms in the maintenance of pain...
December 29, 2017: Scandinavian Journal of Pain
Anke E Kip, Monique Wasunna, Fabiana Alves, Jan H M Schellens, Jos H Beijnen, Ahmed M Musa, Eltahir A G Khalil, Thomas P C Dorlo
The Leishmania parasite resides and replicates within host macrophages during visceral leishmaniasis (VL). This study aimed to evaluate neopterin, a marker of macrophage activation, as possible pharmacodynamic biomarker to monitor VL treatment response and to predict long-term clinical relapse of VL. Following informed consent, 497 plasma samples were collected from East-African VL patients receiving a 28-day miltefosine monotherapy (48 patients) or 11-day combination therapy of miltefosine and liposomal amphotericin B (L-AMB, 48 patients)...
2018: Frontiers in Cellular and Infection Microbiology
Kenta Kikuchi, Mayumi Iida, Naoki Ikeda, Shigetaka Moriyama, Michito Hamada, Satoru Takahashi, Hiroshi Kitamura, Takashi Watanabe, Yoshinori Hasegawa, Koji Hase, Takeshi Fukuhara, Hideyo Sato, Eri H Kobayashi, Takafumi Suzuki, Masayuki Yamamoto, Masato Tanaka, Kenichi Asano
Macrophages manifest distinct phenotype according to the organs in which they reside. In addition, they flexibly switch their character in adaptation to the changing environment. However, the molecular basis that explains the conversion of the macrophage phenotype has so far been unexplored. We find that CD169+ macrophages change their phenotype by regulating the level of a transcription factor Maf both in vitro and in vivo in C57BL/6J mice. When CD169+ macrophages were exposed to bacterial components, they expressed an array of acute inflammatory response genes in Maf-dependent manner and simultaneously start to downregulate Maf...
June 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Kenichi Asano, Kenta Kikuchi, Masato Tanaka
Tissue macrophages comprise heterogeneous subsets that differ in localization, phenotype, and ontogeny. They acquire tissue-specific phenotype in order to maintain normal tissue physiology. This review summarizes the current knowledge about the functions of CD169-positive macrophage subset residing in the lymphoid organs and intestinal tract. Strategically positioned at the interface between tissue and circulating fluid, CD169+ macrophages in the lymphoid organs capture blood- and lymph-borne particulate materials...
June 14, 2018: Journal of Biochemistry
Sicong He, Jiahao Chen, Yunyun Jiang, Yi Wu, Lu Zhu, Wan Jin, Changlong Zhao, Tao Yu, Tienan Wang, Shuting Wu, Xi Lin, Jianan Y Qu, Zilong Wen, Wenqing Zhang, Jin Xu
The origin of Langerhans cells (LCs), which are skin epidermis-resident macrophages, remains unclear. Current lineage tracing of LCs largely relies on the promoter-Cre-LoxP system, which often gives rise to contradictory conclusions with different promoters. Thus, reinvestigation with an improved tracing method is necessary. Here, using a laser-mediated temporal-spatial resolved cell labeling method, we demonstrated that most adult LCs originated from the ventral wall of the dorsal aorta (VDA), an equivalent to the mouse aorta, gonads, and mesonephros (AGM), where both hematopoietic stem cells (HSCs) and non-HSC progenitors are generated...
June 15, 2018: ELife
Ronald S Flannagan, David W Watson, Bas G Surewaard, Paul Kubes, David E Heinrichs
Staphylococcus lugdunensis is a commensal bacterium that can cause serious infection suggesting an ability to circumvent aspects of host immunity. We demonstrate here that macrophages fail to kill ingested S. lugdunensis and the bacteria persist for extended periods, without replicating, within mature LAMP-1-positive phagolysosomes. Phagocytosed S. lugdunensis also do not intoxicate host cells in contrast to S. aureus. Optimal survival of S. lugdunensis requires O-acetylated peptidoglycan since an oatA mutant, which is more sensitive to killing by lysozyme than WT, survived to a lesser extent in macrophages...
June 14, 2018: Cellular Microbiology
Jesse W Williams, Catherine Martel, Stephane Potteaux, Ekaterina Esaulova, Molly A Ingersoll, Andrew Elvington, Brian T Saunders, Li-Hao Huang, Andreas J Habenicht, Bernd H Zinselmeyer, Gwendalyn J Randolph
OBJECTIVE: Macrophages play important roles in the pathogenesis of atherosclerosis, but their dynamics within plaques remain obscure. We aimed to quantify macrophage positional dynamics within progressing and regressing atherosclerotic plaques. APPROACH AND RESULTS: In a stable intravital preparation, large asymmetrical foamy macrophages in the intima of carotid artery plaques were sessile, but smaller rounded cells nearer plaque margins, possibly newly recruited monocytes, mobilized laterally along plaque borders...
June 14, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Tiantian Ye, Yue Wu, Lei Shang, Xueqing Deng, Shujun Wang
Borneol as a penetration enhancer is widely used in guiding other components through the biological barrier into the targeting organs or tissues. This study aimed at studying effect and mechanism of synthetic borneol (S-BO) on improving lymphatic-targeting ability of 7-ethyl-10-hydroxycamptothecin liposomes (SN-38-Lips) via increasing lymph node uptake. At first, SN-38-Lips prepared had appropriate particle distribution, drug loading property and compatible stability with S-BO. Both in vitro cellular uptake and in vivo fluorescence imaging showed that 2 and 5 mg/mL S-BO, especially 2 mg/mL S-BO, enhanced cytoplasmic fluorescence signal of SN-38-Lips in the macrophages based on phagocytosis effect...
November 2018: Drug Delivery
Soo Min Cho, Ayelet Vardi, Nicolas Platt, Anthony H Futerman
Approximately 70 lysosomal storage diseases are currently known, resulting from mutations in genes encoding lysosomal enzymes and membrane proteins. Defects in lysosomal enzymes that hydrolyze sphingolipids have been relatively well studied. Gaucher disease is caused by the loss of activity of glucocerebrosidase, leading to accumulation of glucosylceramide. Gaucher disease exhibits a number of subtypes, with types 2 and 3 showing significant neuropathology. Sandhoff disease results from the defective activity of β-hexosaminidase, leading to accumulation of ganglioside GM2...
June 14, 2018: Journal of Neurochemistry
Scott Seitz, Penny Clarke, Kenneth L Tyler
Flaviviruses account for most arthropod-borne cases of human encephalitis in the world. However the exact mechanisms of injury to the central nervous system (CNS) during Flavivirus infections remain poorly understood. Microglia are the resident immune cell of the CNS and are important for multiple functions, including control of viral pathogenesis. Utilizing a pharmacologic method of microglia depletion (PLX5622, Plexxikon Inc, an inhibitor of colony stimulating factor 1 receptor) we sought to determine the role of microglia in Flaviviral pathogenesis...
June 13, 2018: Journal of Virology
Moumita Adak, Debajyoti Das, Sougata Niyogi, Challa Nagalakshmi, Dipika Ray, Partha Chakrabarti
Hepatocellular death or ballooning distinguishes the transition of simple steatosis to irreversible nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of hepatocellular apoptosis in NASH is largely unclear, and discovery of endogenous mediators that could prevent or inhibit cell death is thereby critical in intercepting NASH progression. Here, we identified pigment epithelium-derived factor (PEDF), a secreted, moonlighting hepatokine as 1 hepatoprotective agent in mice with diet-induced NASH...
June 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Laurence Black, Jeremie M Lever, Amie M Traylor, Bo Chen, Zhengqin Yang, Stephanie Esman, Yanlin Jiang, Gary Cutter, Ravindra Boddu, James George, Anupam Agarwal
Chronic kidney disease (CKD) is a condition with significant morbidity and mortality that affects 15% of adults in the United States. One cause of CKD is acute kidney injury (AKI), which commonly occurs secondary to sepsis, ischemic events, and drug-induced nephrotoxicity. Unilateral ischemia-reperfusion injury (UIRI) without contralateral nephrectomy (CLN) and repeated low dose cisplatin (RLDC) models of AKI to CKD demonstrate responses characteristic of the transition; however, previous studies have not effectively compared the pathogenesis...
June 13, 2018: American Journal of Physiology. Renal Physiology
Jessica M Rosin, Deborah M Kurrasch
BACKGROUND: Since its inception in 2001, in utero electroporation (IUE) has been widely used by the neuroscience community. IUE is a technique developed to introduce plasmid DNA into embryonic mouse brains without permanently removing the embryos from the uterus. Given that IUE labels cells that line the ventricles, including radial fibers and migrating neuroblasts, this technique is an excellent tool for studying factors that govern neural cell fate determination and migration in the developing mouse brain...
June 12, 2018: Journal of Neuroinflammation
Geetika Bajpai, Caralin Schneider, Nicole Wong, Andrea Bredemeyer, Maarten Hulsmans, Matthias Nahrendorf, Slava Epelman, Daniel Kreisel, Yongjian Liu, Akinobu Itoh, Thirupura S Shankar, Craig H Selzman, Stavros G Drakos, Kory J Lavine
Paradigm-shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2- and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here, we demonstrate that the human myocardium also contains distinct subsets of CCR2- and CCR2+ macrophages. Analysis of sex-mismatched heart transplant recipients revealed that CCR2- macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation...
June 11, 2018: Nature Medicine
Neelam Prakash Bodhale, Subhashis Pal, Sunil Kumar, Debprasad Chattopadhyay, Bhaskar Saha, Naibedya Chattopadhyay, Maitree Bhattacharyya
Leishmania donovani is a protozoan parasite that infects mammalian macrophages, wherein the parasite resides and replicates as amastigotes, inflicting the potentially fatal disease visceral leishmaniasis. The disease is characterized by severe immunosuppression and hypocholesterolemia implying metabolic changes in L. donovani infection; whether such metabolic changes are also linked to susceptibility to the infection is not known. Herein, four inbred mouse strains were first characterized for their resistance or susceptibility profile to L...
June 6, 2018: Cytokine
Milena Králíčková, Ludek Fiala, Petr Losan, Pavel Tomes, Vaclav Vetvicka
BACKGROUND: This study was conducted to summarize current knowledge of the changes within the immune system, from action of macrophages, lymphocytes and NK cells to biological effects of their products. Endometriosis is a complex gynecological disorder defined as a presence of endometrial tissue outside the uterus affecting over 5 million reproductive-aged women in the U.S. alone. RESULT: In recent years, the potential role of the immune system in the development of endometriosis has increasingly gained attention...
June 6, 2018: Immunological Investigations
Laura McCulloch, Alessio Alfieri, Barry W McColl
Changes to the immune system after stroke are complex and can result in both pro-inflammatory and immunosuppressive consequences. Following ischemic stroke, brain resident microglia are activated and circulating monocytes are recruited to the injury site. In contrast, there is a systemic deactivation of monocytes/macrophages that may contribute to immunosuppression and the high incidence of bacterial infection experienced by stroke patients. The manipulation of macrophage subsets may be a useful therapeutic strategy to reduce infection and improve outcome in patients after stroke...
2018: Frontiers in Immunology
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