Macrophages belong to the mononuclear phagocyte system that includes the blood monocytes and the various kinds of mobile and sessile macrophages They are recruited from the stem cells of the bone marrow and differentiate under the influence of specific signals [1] [e g the macrophage colonystimulating factor, the granulocyte/macrophage colonystimulating factor and interleukin-3 (IL-3)] via several intermediary stages to mature macrophages [2] (Fig 1) They belong, together with the highly specific immune system, to the body’s defensive machinery Although all macrophages are ultimately derived from the same source (bone marrow) they may in some instances, e g in the liver, also propagate at the site of their final destination [3] Topological factors seem to influence their final differentiation and to endow each type with particular metabolic and structural features One can clearly recognize specific capabilities in the mobile bloodborne macrophages (monocytes), in the individually moving but sequestered (peritoneal and alveolar) macrophages, and in the various sessile tissue macrophages such as those residing in bone marrow, spleen, brain, skin and liver [4,5]

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1990.tb19222.x

Biologically active products of stimulated liver macrophages (Kupffer cells)

Nanoparticle Uptake: The Phagocyte Problem.

Bacterial sepsis and septic shock result from the overproduction of inflammatory mediators as a consequence of the interaction of the immune system with bacteria and bacterial wall constituents in the body. Bacterial cell wall constituents such as lipopolysaccharide, peptidoglycans, and lipoteichoic acid are particularly responsible for the deleterious effects of bacteria. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Within the circulation bacterial constituents interact with proteins such as plasma lipoproteins and lipopolysaccharide binding protein. The interaction of the bacterial constituents with receptors on the surface of mononuclear cells is mainly responsible for the induction of proinflammatory mediators by the bacterial constituents. The role of individual receptors such as the toll-like receptors and CD14 in the induction of proinflammatory cytokines and adhesion molecules is discussed in detail. In addition, the roles of a number of other receptors that bind bacterial compounds such as scavenger receptors and their modulating role in inflammation are described. Finally, the therapies for the treatment of bacterial sepsis and septic shock are discussed in relation to the action of the aforementioned receptors and proteins.

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.

https://journals.sagepub.com/doi/pdf/10.1177/0192623307313011

Long-term Air Pollution Exposure Is Associated with Neuroinflammation, an Altered Innate Immune Response, Disruption of the Blood-Brain Barrier, Ultrafine Particulate Deposition, and Accumulation of Amyloid β-42 and α-Synuclein in Children and Young Adults:

INTRODUCTION 380 SEPSIS AND SEPTIC SHOCK 380 BACTERIAL CELL WALL ARCHITECTURE 381 Lipopolysaccharide 381 Lipoteichoic and Teichoic Acids 383 Peptidoglycan 383 Purification and Aggregate Structure 383 HOST RESPONSE TO CELL WALL CONSTITUENTS 384 Cellular Defense 384 Humoral Defense 385 The Liver 385 Liver cell types 386 Experiments with Radiolabeled Lipopolysaccharide In Vivo 386 Macrophages and the Response to Lipopolysaccharide and Lipoteichoic Acid 386 Detoxification of Lipopolysaccharide 387 LIPOPOLYSACCHARIDE AND LIPOTEICHOIC ACID RECEPTORS 387 Lipopolysaccharide-Binding Protein 388 CD14 388 sCD14 389 Toll-Like Receptors 390 2-Integrins 392 Selectins 393 Scavenger Receptors 393 Moesin 394 Heptose-Specific Lipopolysaccharide Receptor 394 LIPOPOLYSACCHARIDEAND LIPOTEICHOIC ACID-BINDING PROTEINS 394 Neutrophilic Lipopolysaccharide-Binding Molecules 394 Bactericidal/permeability-increasing protein 394 CAP18 394 CAP37 395 Lactoferrin 395 Lysozyme 395 Other Lipopolysaccharide-Binding Proteins 395 Development of Bactericidal and Lipopolysaccharide-Neutralizing Peptides 395 LIPOPROTEINS 395 Metabolism 395 Apolipoprotein E 396 Anti-Inflammatory Role 396 Lipid Metabolism and Infection 398 CLINICAL AND EXPERIMENTAL SEPSIS THERAPIES 399 Immunosuppression and Neutralization of Proinflammatory Cytokines 400 CONCLUDING REMARKS 400 REFERENCES 401

https://biorxiv.org/content/biorxiv/early/2016/04/07/047647.full.pdf

Publisher Summary The study of Kupffer cells has developed rapidly and has been extended to problems concerning the origin, structure, and function of these cells in normal and pathological conditions This chapter provides an overview of the current morphological and biochemical data. Many of the major advances in Kupffer cells have resulted from the development of new methods, such as cell isolation, purification, and culture. Kupffer cells play a major role in the clearance of endotoxin from the blood, which induces the release of a number of mediators. Experimental virus infections provide the indications of the viral hepatitis development in human liver. The susceptibility of Kupffer cells to bacterial and viral infections is influenced by hormonal, immunological, nutritional, and genetic factors. The regulatory role of Kupffer cells in various hepatic disorders as well as in liver transplantation still requires further investigation. The chapter discusses the involvement of Kupffer cells and natural killer (NK) cells in the defense against tumor development and describes the way in which Kupffer cells coordinate their activities with liver-associated NK cells in tumor cell cytotoxicity. Since the descriptions of the isolation, purification, and culture of Kupffer cells from rat liver, the study of the function of these cells in vitro has made considerable progress.

R.s. Mccuskey

Papers

Cell biology and kinetics of Kupffer cells in the liver.

Tenascin synthesis in cultured rat liver fat-storing cells.

Pit cell and Kupffer cell reactions in rats treated with systemic or hepatic continuous infusion of interleukin-2.

Characterization of a liver-specific population of large granular lymphocytes (LGL) or pit cells.