Cooperation of antigens,immunoglobulins, complement,and antimicrobial enzymes in regulation of mobility of blood granulocytes

Cooperation between specific and nonspecific factors of humoral immunity in the regulation of granulocyte mobility was studied. Bacterial antigens of dental plaque, immunoglobulins, lysozyme, peroxidase, ribonuclease, and trypsin, each separately, were shown to produce moderate stimulation of chemotaxis and chemokinesis of granulocytes. The strongest chemotaxic effect was given by ribonuclease and the strongest chemokinetic effect by lysozyme. The strongest chemotaxic stimulus was generated on activation by complement in the classical way. Lysozyme sharply enhanced whereas ribonuclease and trypsin depressed the formation of the chemotaxis factor of complement in the classical way. Treatment of granulocytes with antimicrobial enzymes lowered their sensitivity to this factor.Laboratory of Pathophysiology, Research Institute of Stomatology, Ministry of Health of the Ukrainian SSR, Odessa. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 1, pp. 40–42, January, 1980.     

Dibutyltin‐induced alterations of interleukin 1beta secretion from human immune cells

Dibutyltin (DBT) is used to stabilize polyvinyl chloride plastics (including pipes that distribute drinking water) and as a de‐worming agent in poultry. DBT is found in human blood, and DBT exposures alter the secretion of tumor necrosis factor alpha and interferon gamma from lymphocytes. Interleukin (IL)‐1β is a proinflammatory cytokine that regulates cellular growth, tissue restoration and immune response regulation. IL‐1β plays a role in increasing invasiveness of certain tumors. This study reveals that exposures to DBT (24 h, 48 h and 6 days) modify the secretion of IL‐1β from increasingly reconstituted preparations of human immune cells (highly enriched human natural killer cells, monocyte‐depleted [MD] peripheral blood mononuclear cells [PBMCs], PBMCs, granulocytes and a preparation combining both PBMCs and granulocytes). DBT altered IL‐1β secretion from all cell preparations. Higher concentrations of DBT (5 and 2.5 μm ) decreased the secretion of IL‐1β, while lower concentrations of DBT (0.1 and 0.05 μm ) increased the secretion of IL‐1β. Selected signaling pathways were examined in MD‐PBMCs to determine if they play a role in DBT‐induced elevations of IL‐1β secretion. Pathways examined were IL‐1β converting enzyme (caspase 1), mitogen‐activated protein kinases and nuclear factor kappa B. Caspase 1 and mitogen‐activated protein kinase pathways appear to be utilized by DBT in increasing IL‐1β secretion. These results indicate that DBT alters IL‐1β secretion from human immune cells in an ex. vivo system utilizing several IL‐1β regulating signaling pathways. Thus, DBT may have the potential to alter IL‐1β secretion in an in vivo system. Copyright © 2016 John Wiley & Sons, Ltd.     

In vitro immunomodulatory activity of Filipendula ulmaria

Extracts of the roots, herb and flowers of Filipendula ulmaria (L.) Maxim. were investigated for in vitro immunomodulatory properties. Strong inhibitory activity was found towards the classical pathway of complement in the ethyl acetate extracts of roots and flowers, in all methanol extracts and in the aqueous root extract. Except for the light-petroleum extracts, all fractions tested inhibited the production of reactive oxygen species by human polymorphonuclear leukocytes. The diethyl ether root extract was found to be most potent in inhibiting lymphocyte proliferation. The role of tannins and other constituents in these processes are discussed. © 1997 John Wiley & Sons, Ltd.     

哮喘患者支气管诱导痰液中炎性细胞的分析研究

目的研究哮喘患者急性发作期及缓解期痰液中炎性细胞的变化。方法留取哮喘患者发作期和缓解期支气管诱导痰液,检测其细胞成分并与对照组相比较。结果哮喘患者急性发作期诱导痰液的中性粒细胞数较其缓解期和对照组均明显增高,嗜酸性粒细胞数与哮喘急性发作期和缓解期均较对照组明显增高,巨噬细胞数与哮喘各期均较对照组明显降低。结论哮喘病是一种慢性气道炎症性疾病,在不同发病时期气道内的炎性细胞变化不同。     

Study of morphology and rigidity of neutrophilic granulocyte membrane in the real time mode by scanning probe microscopy

The rigidity of neutrophilic granulocyte membrane was determined: 2.1±0.7 kPa. Scanning in the contact mode did not modify cell morphology, while spectroscopy caused nonspecific swelling reaction and a 3-fold increase in cell volume. Spectroscopy had no effect on rigidity of neutrophilic granulocyte membrane. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 6, pp. 712–714, June, 2006     

Polymorphonuclear leucocytes selectively produce anti-inflammatory interleukin-1 receptor antagonist and chemokines, but fail to produce pro-inflammatory mediators

The role of neutrophils in the immune response has long been regarded as mainly phagocytic, but recent publications have indicated the production of several cytokines by polymorphonuclear leucocytes (PMN). The results of the individual reports, however, vary considerably. In this study, we established a cytokine profile of pure human neutrophils and demonstrated that minor contamination of peripheral blood mononuclear cells (PBMCs) in PMN preparations can lead to false-positive results. In our hands, peripheral blood PMN fail to produce the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Instead, they secrete large amounts of the chemokine IL-8 and the anti-inflammatory IL-1 receptor antagonist (IL-1ra). Additionally, PMN preparations of a high purity show production of the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and growth-related oncogene-alpha (GRO-alpha), as well as macrophage colony-stimulating factor (M-CSF). The neutrophil therefore represents a novelty by producing the antagonist of IL-1beta (i.e. IL-1ra) in the absence of IL-1beta itself. To support our results, we differentiated stem cells from human cord blood into PMN and monocytes, respectively. These in vitro-differentiated PMN showed the same cytokine profile as peripheral blood PMN lacking IL-1beta, while differentiated monocytes produced the expected IL-1beta in addition to IL-1ra. The clear anti-inflammatory nature of their cytokine profile enables PMN to antagonize pro-inflammatory signals in experimental conditions. It is therefore possible that PMN play a key role in immune regulation by counteracting a dysregulation of the inflammatory process. Clinical studies, in which administration of recombinant G-CSF had a favourable effect on the outcome of severe infections and even sepsis without worsening inflammation, could thus be explained by our results.     

A new paradigm of eosinophil granulocytes: neuroimmune interactions

Abstract:  Eosinophil granulocytes have long been regarded as potent effector cells with the potential to release an array of inflammatory mediators involved in cytotoxicity to helminths and tissue destruction in chronic inflammatory diseases such as asthma. However, it has become evident that eosinophils are also involved in regulatory mechanisms modulating local tissue immune responses. Eosinophils take part in remodelling and repair mechanisms and contribute to the localized innate and acquired immune response as well as systemic adaptive immunity. In addition, eosinophils are involved in neuroimmune interactions modulating the functional activity of peripheral nerves. Neuromediators can also modulate the functional activity of eosinophils, revealing bidirectional interactions between the two cell types. Eosinophils are tissue-resident cells and have been found in close vicinity of peripheral nerves. This review describes neuroimmune interactions between eosinophil granulocytes and peripheral nerves and highlights why eosinophils are important in allergic diseases such as asthma.     

The distribution of choline acetyltransferase- and acetylcholinesterase-like immunoreactivity in the palmar skin of patients with palmoplantar pustulosis

The distribution of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in involved skin in patients with palmoplantar pustulosis (PPP) and in normal palmar skin in healthy non-smokers and smokers has been studied by immunohistochemistry, especially in relation to the sweat gland apparatus. The sweat gland and its duct showed ChAT- and AChE-like immunoreactivity (LI) of varying intensity in all three groups and with stronger reactivity than in the epidermis. ChAT-LI was present in the coil and in the duct except in the corneal layer. Smokers and patients with PPP displayed significantly fewer ChAT+ acrosyringia than non-smokers. In the patients with PPP, the granulocytes in the pustules and in the papillary dermis displayed ChAT-LI. Western blot analysis of granulocytes from peripheral blood from healthy donors confirmed the presence of ChAT-like proteins in large amounts in neutrophils and small amounts in eosinophils. AChE-LI of varying intensity was found in all parts of the sweat gland apparatus in all three groups. The strongest AChE-LI in the acrosyringia was seen in the lowest part of the stratum corneum, where the PPP pustules are located. No significant differences in staining pattern or intensity were found between the coils, nerve fibres surrounding the coils or ducts. The number of mast cells in the papillary dermis was about four times larger in the patients with PPP than in the control subjects. AChE-LI was observed in about 25% of the mast cells in non-smoking control subjects and in patients with PPP, but only in 10% of those in the smoking control subjects. Our findings indicate that the (non-neuronal) cholinergic system may be involved in cutaneous inflammatory processes.     

The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study

BACKGROUND: While many studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have investigated the effects of tacrolimus on inflammatory cells and their cytokine gene expression in patients with AD. OBJECTIVES: To characterize further the immunophenotype of infiltrating cells and the production of certain cytokines before and after treatment with topical tacrolimus and hydrocortisone butyrate. METHODS: Nine adult patients with moderate to severe AD were treated with tacrolimus ointment, while seven control patients were treated with hydrocortisone butyrate ointment. We performed lesional skin biopsies before and after treatment. These were stained immunohistochemically with a panel of monoclonal antibodies including those to CD1a, CD3, CD4, CD8, myeloperoxidase, EG1, EG2, tryptase, interferon-gamma, interleukin (IL)-4, IL-5, IL-12, IL-13, receptors for CXC chemokines (CXCR) 3 and 4, and receptor 3 for CC chemokines. RESULTS: CD3+, CD4+ and CD8+ lymphocytes, and eosinophil and neutrophil granulocytes were significantly reduced in post-treatment tacrolimus specimens, while CD1a+ cells and mast cells were not. The expression of cytokines and chemokine receptors tested, except for CXCR3, was diminished by tacrolimus treatment. Moreover, tacrolimus produced a greater reduction of lymphocytes, eosinophils and most cytokines than that induced by hydrocortisone butyrate. CONCLUSIONS: Tacrolimus not only inhibits T-lymphocyte proliferation and cytokine production, but also plays an important role in the IL-12-induced shift from a T-helper (Th) 2 to a Th1 cytokine profile that characterizes the development of chronic AD. Tacrolimus also demonstrates wider pharmacodynamic effects than hydrocortisone.     

Apoptosis driven infection

Professional phagocytes like polymorphonuclear neutrophil granulocytes (PMN) and macrophages (MF) kill pathogens as the first line of defense. These cells possess numerous effector mechanisms to eliminate a threat at first contact. However, several microorganisms still manage to evade phagocytic killing, survive and retain infectivity. Some pathogens have developed strategies to silently infect their preferred host phagocytes. The best example of an immune silencing phagocytosis process is the uptake of apoptotic cells. Immune responses are suppressed by the recognition of phosphatidylserine (PS) on the outer leaflet of their plasma membrane. Taking Leishmania major as a prototypic intracellular pathogen, we showed that these organisms can use the apoptotic “eat me” signal PS to silently enter PMN. PS-positive and apoptotic parasites, in an altruistic way, enable the intracellular survival of the viable parasites. Subsequently these pathogens again use PS exposition, now on infected PMN, to silently invade their definitive host cells, the MF. In this review, we will focus on L. major evasion strategies and discuss other pathogens and their use of the apoptotic “eat me” signal PS to establish infection.