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Host Defenses Against Prototypical Intracellular Protozoans, the Leishmania
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
Richard D. Pearson, Mary E. Wilson
Murray and co-workers (102,187) reported that coneanavalin A-elicited lymphokines could activate human monocyte-derived macrophages to kill L. donovani amastigotes. Antibodies against interferon-gamma abrogated this macrophage activating factor (MAF) activity. They then demonstrated that exposure of human macrophages to recombinant interferon-gamma also resulted in intracellular killing of L. donovani amastigotes, and concluded that interferongamma was primarily responsible for MAF activity in their system (187). The importance of interferon-gamma in activating macrophages to kill Leishmanial has been confirmed by many groups (188-192). Carvalho et al. (193) subsequently demonstrated that production of interferon-gamma and interleukin 2 in response to leishmanial antigens was absent during active visceral leishmaniasis but was restored after chemotherapy. The failure of T cells to produce interferon-gamma in response to L. donovani is thought to represent a key defect in the immune response during visceral leishmaniasis.
Histoplasmosis
Published in Rebecca A. Cox, Immunology of the Fungal Diseases, 2020
Macrophage activating factor (MAF) — H. capsulatum is a facultative intracellular parasite of the cells of the reticuloendothelial system.3,4–6 The intracellular behavior of the fungus in cells in vitro has been studied by a number of investigators.68–71,99,173,201–204 Extension of such studies to immunized animals revealed that mononuclear phagocytes from the peritoneal cavity of mice immunized against H. capsulatum restrict the intracellular growth of the fungus.72,173,190,205 Moreover, growth of the fungus within normal macrophages is inhibited by lymphocytes freshly harvested from immunized mice.190,205 Therefore, immune lymphocytes acting as mediator cells of acquired immunity can activate normal macrophages to inhibit the intracellular growth of H. capsulatum. Activation is mediated by lymphokines generated in cultures of immune splenocytes stimulated with Histoplasma antigen.88 Treatment of the immune splenocytes with anti-Thy 1 plus complement abolishes lymphokine production; hence, MAF is produced by immune T cells.88 Supernatants from concanavalin A-stimulated T-cell hybridomas also activate macrophages to suppress the intracellular growth of H. capsulatum89 (Table 1).
Host-Parasite Interactions With Macrophages In Culture
Published in Hans H. Gadebusch, Phagocytes and Cellular Immunity, 2020
Lee S. F. Soderberg, Morris Solotorovsky
Specifically armed cytotoxic macrophages have been shown to become nonspecifically cytotoxic when exposed to the specific antigen.198 Macrophages specifically cytotoxic for SL2 lymphoma cells became nonspecifically cytotoxic for SL2 or TLX9 lymphoma cells when incubated for 4 hr with SL2 cells, but not TLX9 cells. Macrophages specifically cytotoxic for TLX9 cells only killed SL2 cells when preincubated with TLX9 cells. Macrophages sensitized with BCG were cytotoxic for both tumor cell lines only when exposed to PPD first. The relationship of tumor cell killing to killing of intracellular parasites by macrophages involves both similar and dissimilar interactions. Both specific and nonspecific tumor cell killing are apparently extracellular, and phagocytosis is a late event that occurs only after cell death. There are similarities between intracellular microbe killing and extracellular tumor-cell killing. In both cases a soluble factor is apparently released from a specifically sensitized lymphocyte, probably a T cell, when incubated with the antigen. Nonspecific lymphocyte stimulation such as mitogen or allogeneic stimulation can also cause release of such factors. Normal macrophages treated with such factors become physiologically activated. Whether specific macrophage arming factor is the same as nonspecific macrophage activating factor is unresolved. Chemical purification techniques will resolve this problem and better define these mechanisms of macrophage activation.
Group-specific component exon 11 haplotypes (D432E and T436K) and risk of albuminuria in type 2 diabetes mellitus patients
Published in Archives of Physiology and Biochemistry, 2022
Manal S. Fawzy, Eman A. Toraih, Essam Al Ageeli, Abeer M. Mohamed, Baraah T. Abu AlSel, Shahad W. Kattan, Walla Alelwani
GC gene is under the control of an autonomous regulatory region. It forms a single polypeptide chain of 474 amino acids with a molecular mass of 52.964 kDa. Alternative transcript splicing can produce three isoforms. The first one (P02774-2) is considered the canonical sequence, made up of two parts; a signal peptide 16 amino acids at the amino-terminal and the main chain of 458 amino acids long. The second isoform (P02774-2; 352 amino acids) missed the first 122 amino acids and is produced at very low levels, whereas, the isoform 3 (P02774-3; 493 amino acids) contains extra 19 amino acids at the amino-terminal of the protein. VDBP undergoes two post-translational modifications; (a) disulphide bonds at 14 different locations forming 9 double loops that determine the triple-domain structure of VDBP and (b) O-glycosylation at the threonine residue at position 436. This conversion is thought to produce a macrophage-activating factor.
Bioinformatics analysis on differentially expressed genes of alveolar macrophage in IPF
Published in Experimental Lung Research, 2019
Huaibin Wang, Miaomiao Wang, Kun Xiao, Xu Zhang, Peng Wang, Shuyu Xiao, Huisheng Qi, Lijun Meng, Xiujun Zhang, Fuhai Shen
SPP1 is the most up-regulated, and has been proved to be closely related to IPF. The protein encoded by SPP1 gene (secreted phosphoprotein 1) not only participates in the connection between osteoclast and mineralized bone matrix, but also as a cytokine involved in enhancing the production of interferon gamma and interleukin-12, reducing the production of interleukin-10, and plays an important role in the pathway of I type immunization. Zhang et al. have proved that the levels of fibronectin 1 (FN1) and secreted phosphoprotein 1 (SPP1) were significantly increased in fibrotic lungs.31 Moreover, the expression of the protein encoded by SPP1 in the lungs of fibrotic mice induced by silica increased correspondingly.32 Due to the gradual development of IPF, the inflammation is aggravated and the secretion of cytokines is increased. Macrophages appear in the focus of the lesion and remove the pathogenic factors under the action of the macrophage activating factor. At the same time, inflammation triggers the immune system of the body. IL-12 stimulates the proliferation of activated T cells and induces the cytotoxic activity of CTL and NK cells, and promotes its secretion of IFN- gamma, TNF- alpha, GM-CSF, and other cytokines to strengthen the immunization. IL-10 also protects human monocytes and macrophages from complement cleavage by inhibiting the killing of microorganisms’ uptake. Therefore, the protein encoded by SPP1 is continuously released as a cytokine and stimulates various immune responses to deal with IPF induced injury. The increased expression of SPP1 in alveolar macrophages may indicate potential IPF.
The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis
Published in Gynecological Endocrinology, 2021
Abolfazl Mehdizadehkashi, Samaneh Rokhgireh, Kobra Tahermanesh, Neda Eslahi, Sara Minaeian, Mansooreh Samimi
Our study also showed that vitamin D supplementation for 12 weeks improved total-/HDL-cholesterol ratio in women with endometriosis significantly. Recent data have shown that macrophage activation is complicated in endometriosis pathogenesis. Additionally, abnormal cholesterol fractions found to act as an important macrophage activating factor. Thus, vitamin D supplementation may affect endometriosis patients positively via improving cholesterol metabolism [39]. Based on our results, vitamin D intake for 12 weeks led to a significant decrease in hs-CRP levels and a significant increase in TAC concentration of patients with endometriosis. Increased levels of various factors including adhesion, angiogenic, and growth factors as well as several pro-inflammatory cytokines have been detected in serum and endometrium of women with endometriosis [40]. Moreover, oxidative stress which is involved in inflammation processes has been found to play role in endometriosis pathogenesis [41,42]. In endometriosis pathogenesis, activated macrophages involved in the degradation of erythrocytes leading to releasing of pro-inflammatory and pro-oxidant mediators [43]. According to these data, the role of inflammation along with oxidative stress is important in the progression of endometriosis. Anti-inflammatory and antioxidant effects of vitamin D have been reported in several disorders such as diabetic fool ulcer [44], chronic kidney diseases [45], polycystic ovarian syndrome [46], and gestational diabetes [47], an in vitro study showed the anti-inflammatory effects of vitamin D on human endometriotic stromal cells. The results of this study indicated that vitamin D decreased IL-1 and TNF-α as well as IL-8 and prostaglandins activities. Moreover, NF-kB pathway inhibited by vitamin D [20].