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There have been recent extensive studies and rapid advancement on the pathogenesis underlying idiopathic pulmonary fibrosis (IPF), and intricate pathogenesis of IPF has been suggested. The purpose of this study was to clarify the logical relationship between these mechanisms. An extensive search was undertaken of the PubMed using the following keywords: “etiology,” “pathogenesis,” “alveolar epithelial cell (AEC),” “fibroblast,” “lymphocyte,” “macrophage,” “epigenomics,” “histone,” acetylation,” “methylation,” “endoplasmic reticulum stress,” “mitochondrial dysfunction,” “telomerase,” “proteases,” “plasminogen,” “epithelial-mesenchymal transition,” “oxidative stress,” “inflammation,” “apoptosis,” and “idiopathic pulmonary fibrosis.” This search covered relevant research articles published up to April 30, 2020. Original articles, reviews, and other articles were searched and reviewed for content; 240 highly relevant studies were obtained after screening. IPF is likely the result of complex interactions between environmental, genetic, and epigenetic factors: environmental exposures affect epigenetic marks; epigenetic processes translate environmental exposures into the regulation of chromatin; epigenetic processes shape gene expression profiles; in turn, an individual's genetic background determines epigenetic marks; finally, these genetic and epigenetic factors act in concert to dysregulate gene expression in IPF lung tissue. The pathogenesis of IPF involves various imbalances including endoplasmic reticulum, telomere length homeostasis, mitochondrial dysfunction, oxidant/antioxidant imbalance, Th1/Th2 imbalance, M1–M2 polarization of macrophages, protease/antiprotease imbalance, and plasminogen activation/inhibition imbalance. These affect each other, promote each other, and ultimately promote AEC/fibroblast apoptosis imbalance directly or indirectly. Excessive AEC apoptosis and impaired apoptosis of fibroblasts contribute to fibrosis. IPF is likely the result of complex interactions between environmental, genetic, and epigenetic factors. The pathogenesis of IPF involves various imbalances centered on AEC/fibroblast apoptosis imbalance.

The article "Reducing macrophage numbers alleviates temporomandibular joint ankylosis", written by Lu Zhao, E Xiao, Linhai He, Denghui Duan, Yang He, Shuo Chen, Yi Zhang and Yehua Gan, was originally published electronically on the publisher's internet portal.

Background For analysis of the tumor microenvironment in diffuse large B-cell lymphoma (DLBCL) tissue samples, it is desirable to obtain information about counts and distribution of different macrophage subtypes. Until now, macrophage counts are mostly inferred from gene expression analysis of whole tissue sections, providing only indirect information. Direct analysis of immunohistochemically (IHC) fluorescence stained tissue samples is confronted with several difficulties, e.g. high variability of shape and size of target macrophages and strongly inhomogeneous intensity of staining. Consequently, application of commercial software is largely restricted to very rough analysis modes, and most macrophage counts are still obtained by manual counting in microarrays or high power fields, thus failing to represent the heterogeneity of tumor microenvironment adequately. Methods We describe a Rudin-Osher-Fatemi (ROF) filter based segmentation approach for whole tissue samples, combining floating intensity thresholding and rule-based feature detection. Method is validated against manual counts and compared with two commercial software kits (Tissue Studio 64, Definiens AG, and Halo, Indica Labs) and a straightforward machine-learning approach in a set of 50 test images. Further, the novel method and both commercial packages are applied to a set of 44 whole tissue sections. Outputs are compared with gene expression data available for the same tissue samples. Finally, the ROF based method is applied to 44 expert-specified tumor subregions for testing selection and subsampling strategies. Results Among all tested methods, the novel approach is best correlated with manual count (0.9297). Automated detection of evaluation subregions proved to be fully reliable. Comparison with gene expression data obtained for the same tissue samples reveals only moderate to low correlation levels. Subsampling within tumor subregions is possible with results almost identical to full sampling. Mean macrophage size in tumor subregions is 152.5±111.3 μm2. Conclusions ROF based approach is successfully applied to detection of IHC stained macrophages in DLBCL tissue samples. The method competes well with existing commercial software kits. In difference to them, it is fully automated, externally repeatable, independent on training data and completely documented. Comparison with gene expression data indicates that image morphometry constitutes an independent source of information about antibody-polarized macrophage occurence and distribution. Electronic supplementary material The online version of this article (10.1186/s12575-019-0098-9) contains supplementary material, which is available to authorized users.

Evidence supports the theory that bacterial communities colonizing Echinacea purpurea contribute to the innate immune enhancing activity of this botanical. Previously, we reported that only about half of the variation in in vitro monocyte stimulating activity exhibited by E. purpurea extracts could be accounted for by total bacterial load within the plant material. In the current study, we test the hypothesis that the type of bacteria, in addition to bacterial load, is necessary to fully account for extract activity. Bacterial community composition within commercial and freshly harvested (wild and cultivated) E. purpurea aerial samples was determined using high-throughput 16S rRNA gene pyrosequencing. Bacterial isolates representing 38 different taxa identified to be present within E. purpurea were acquired, and the activity exhibited by the extracts of these isolates varied by over 8000-fold. Members of the Proteobacteria exhibited the highest potency for in vitro macrophage activation and were the most predominant taxa. Furthermore, the mean activity exhibited by the Echinacea extracts could be solely accounted for by the activities and prevalence of Proteobacteria members comprising the plant-associated bacterial community. The efficacy of E. purpurea material for use against respiratory infections may be determined by the Proteobacterial community composition of this plant, since ingestion of bacteria (probiotics) is reported to have a protective effect against this health condition.

Overcrowding conditions and temperatures shifts regularly manifest in large-scale infections of farmed fish, resulting in economic losses for the global aquaculture industries. Increased understanding of the functional mechanisms of fish antimicrobial host defenses is an important step forward in prevention of pathogen-induced morbidity and mortality in aquaculture setting. Like other vertebrates, macrophage-lineage cells are integral to fish immune responses and for this reason, much of the recent fish immunology research has focused on fish macrophage biology. These studies have revealed notable similarities as well as striking differences in the molecular strategies by which fish and higher vertebrates control their respective macrophage polarization and functionality. In this review, we address the current understanding of the biological mechanisms of teleost macrophage functional heterogeneity and immunity, focusing on the key cytokine regulators that control fish macrophage development and their antimicrobial armamentarium.

Dust, known as “airborne particles”, refers to solid particles that are suspended in air (diameter ≤ 100 μm). Among them, dust with diameter < 2.5 μm, known as “fine particulate matter”, is referred to as PM2.5. After being inhaled by the human body, PM2.5 can directly enter the blood through the bronchi and alveoli, which are phagocytized by macrophage. Their long-term stay in the alveoli exerts a negative impact on the human cardiovascular, nervous system, and other organs, posing a threat to people’s health. Consequently, indoor air quality has become a great concern.

Macrophage behavior is of great interest in response to tissue injury and promotion of regeneration. With increasing numbers of zebrafish reporter-based assays, new capabilities now exist to characterize macrophage migration, and their responses to biochemical cues, such as reactive oxygen species. Real time detection of macrophage behavior in response to oxidative stress using quantitative measures is currently beyond the scope of commercially available software solutions, presenting a gap in understanding macrophage behavior. To address this gap, we developed an image analysis pipeline solution to provide real time quantitative measures of cellular kinetics and reactive oxygen species content in vivo after tissue injury. This approach, termed Zirmi, differs from current software solutions that may only provide qualitative, single image analysis, or cell tracking solutions. Zirmi is equipped with user-defined algorithm parameters to customize quantitative data measures with visualization checks for an analysis pipeline of time-based changes. Moreover, this pipeline leverages open-source PhagoSight, as an automated keyhole cell tracking solution, to avoid parallel developments and build upon readily available tools. This approach demonstrated standardized space- and time-based quantitative measures of (1) fluorescent probe based oxidative stress and (2) macrophage recruitment kinetic based changes after tissue injury. Zirmi image analysis pipeline performed at execution speeds up to 10-times faster than manual image-based approaches. Automated segmentation methods were comparable to manual methods with a DICE Similarity coefficient > 0.70. Zirmi provides an open-source, quantitative, and non-generic image analysis pipeline. This strategy complements current wide-spread zebrafish strategies, for automated standardizations of analysis and data measures.

Reticulo-endothelial macrophages are central for the regulation of iron homeostasis, thanks to their ability to recycle red blood cell-derived iron. Macrophages are also key innate immune cells which exhibit remarkable functional plasticity. These two roles are tightly interconnected: on the one hand, macrophage polarisation dictates the expression of iron-regulated genes and determines cell iron handling; on the other, iron availability affects immune effector functions. Recent observations support a role for free haem and iron in shaping macrophage plasticity towards an M1-like pro-inflammatory phenotype. These findings have implications for the pathophysiology of sickle cell disease, hallmarked by haemolysis and elevated circulating haem and iron, as well as for the tumour microenvironment, characterised by haemolytic red blood cell extravasation and iron-loaded macrophages. Consistently, haem scavenging suppresses the pro-inflammatory profile of macrophages, reducing chronic inflammation in sickle cell disease, whereas nanoparticle-mediated iron delivery to the tumour microenvironment elicits pro-inflammatory macrophages with tumour killing properties, thus delaying tumour growth. This line of research paved the way for the therapeutic modulation of macrophage plasticity achievable through the application of different iron sources or scavengers/chelators according to the desired beneficial effect.

Summary: The Macrophage Pathway Knowledgebase (MACPAK) is a computational system that allows biomedical researchers to query and study the dynamic behaviors of macrophage molecular pathways. It integrates the knowledge of 230 reviews that were carefully checked by specialists for their accuracy and then converted to 230 dynamic mathematical pathway models. MACPAK comprises a total of 24 009 entities and 12 774 processes and is described in the Cell System Markup Language (CSML), an XML format that runs on the Cell Illustrator platform and can be visualized with a customized Cytoscape for further analysis. Availability: MACPAK can be accessed via an interactive web site at http://macpak.csml.org. The CSML pathway models are available under the Creative Commons license. Contact: masao@hgc.jp

The effects of salinity adaptation and ration size on macrophage phagocytosis were assessed in black sea bream (Mylio macrocephalus) juveniles. Salinity had no effect on phagocytosis in fish that were fed a 10% ration size. Reducing ration size from 10 to 5% resulted in a significant reduction in splenic and pronephric macrophage phagocytosis of fish adapted to hyper-(33 p.p.t.) and hypo-osmotic (6 p.p.t.) salinities. The fish that were adapted to an iso-osmotic salinity (12 p.p.t.) and fed a 5% ration size were able to maintain macrophage phagocytic activity at levels comparable to those of fish that were fed a 10% ration size. It is proposed that the adaptation of sea bream to an iso-osmotic medium is beneficial in that it stimulates the immune response through activation of macrophage phagocytosis.

The primary function of the immune system, to say it in the most elemental (and oversimplified, but not altogether untrue) terms, is to distinguish between what is self and what is non-self, and then to eliminate the non-self. Thus, whenever a non-self substance breaks the normal skin and membrane barriers of the body and gets “inside the walls,” the immune system shifts into gear to meet the challenge. If the invader is a microbe, such as a bacterium or virus, macrophage cells seek it out, surround it, and try to ingest and absorb it. They then transport portions of it over to another cell in the system, the T4 cell, the cell that oversees and regulates the entire cellular and humoral immune response, and present the surface of that invader to the surface of the T4 cell for recognition. “See what I have here?” it seems to say. “Well, there are more out there just like this one, and they have the same coat this one has. Let’s gear up for them, train our troops to recognize them, and fight them off. What say? Should we get to battle stations?”1

Air pollution is associated with a high burden or morbidity and mortality, but exposure cannot be quantified rapidly or cheaply. The particulate burden of macrophages from induced sputum may provide a biomarker. We compare the feasibility of two methods for digital quantification of airway macrophage particulate load. Induced sputum samples were processed and analysed using ImageJ and Image SXM software packages. We compare each package by resources and time required. 13 adequate samples were obtained from 21 patients. Median particulate load was 0.38 μm2 (ImageJ) and 4.0 % of the total cellular area of macrophages (Image SXM), with no correlation between results obtained using the two methods (correlation coefficient = −0.42, p = 0.256). Image SXM took longer than ImageJ (median 26 vs 54 mins per participant, p = 0.008) and was less accurate based on visual assessment of the output images. ImageJ’s method is subjective and requires well-trained staff. Induced sputum has limited application as a screening tool due to the resources required. Limitations of both methods compared here were found: the heterogeneity of induced sputum appearances makes automated image analysis challenging. Further work should refine methodologies and assess inter- and intra-observer reliability, if these methods are to be developed for investigating the relationship of particulate and inflammatory response in the macrophage.

This book suffers from the defects of many publications of symposia or special meetings. It details some papers presented at a meeting held in May 1970 on various aspects of cell mediated immunity. This is an extremely fast moving field and although the basic information in the text is correct, much of it, particularly interpretations and understanding of mechanisms, have been altered considerably by information available since May 1970. The review of Valentine on "The Transformation and Proliferation of Lymphocytes 'in Vitro' " does not give sufficient chemical or biochemical background on the various nonspecific stimulants. There is a good review on "Inhibition of Macrophage Migration" by Lamelin. The review by Wolstencroft, particularly in relation to the "Lymphokines," does not provide the reader with the most up-to-date information. The section by Revillard on the "Clinical Applications of 'in Vitro' Tests" is a useful compilation of data that have been very