Rate of Interaction of IgG1 and IgG3 Sensitized Red Cells with Monocytes in the Phagocytosis Assay

Another aspect of the preferential binding to monocytes of IgG3-coated erythrocytes over IgG1-coated erythrocytes has been demonstrated by measuring the rate of interaction in the phagocytosis assay. Erythrocytes sensitized with comparable numbers of IgG1 and IgG3 monoclonal and polyclonal anti-D antibodies were incubated with a monocyte preparation for up to 2 h. Interaction with the erythrocytes sensitized with monoclonal or polyclonal IgG3 was much more rapid than with erythrocytes sensitized with IgG1. With IgG3-sensitized erythrocytes maximum interaction was found after 30 min, whereas with IgG1-sensitized erythrocytes 2 h were required for maximum interaction. These results are consistent with the longer hinge region of IgG3 allowing bridges to be formed more easily between the negatively charged erythrocytes and monocytes.     

The release of inflammatory mediators from neutrophils

Summary Human polymorphonuclear leukocytes exposed to phagocytic stimuli undergo a series of cellular reactions designed to eliminate foreign invaders such as bacteria, viruses, or fungi. The responses of human granulocytes to the stimuli of phagocytosis are initiated at the cell surface and proceed in the following sequence: a. ligand binding to surface receptors; b. membrane hyperpolarization; c. O ₂ ⁻ generation by a surface oxidase and¹O₂ metabolism; d. generation of thromboxanes and prostaglandins; e. lysosomal enzyme secretion. These events, known as ‘stimulus-secretion coupling’, result in the secretion of toxic substances which, though intended to end up in the phagocytic vacuole, may escape to the extracellular space where they initiate inflammation.     

沙棘油抗肿瘤作用及对小鼠NK和单核-巨噬细胞活性的影响

目的研究沙棘油的抗肿瘤作用及对小鼠NK细胞活性、单核-巨噬细胞吞噬功能的影响。方法第一组昆明种雌性健康小鼠136只,进行动物移植性肿瘤抑制实验。第二组选用108只BalB/c雌性健康小鼠进行免疫指标测定,其中48只进行NK细胞活性测定;另外60只小鼠作腹腔巨噬细胞吞噬鸡红细胞实验。两组均经口给予小鼠(1g/kg体重/d;0.33g/kg体重/d;0.033g/kg体重/日;0g/kg)沙棘油。结果给予小鼠1g/kg体重/日的沙棘油30d(接种肿瘤细胞前后均给予受试物),可对荷瘤小鼠S-180肿瘤的生长有抑制作用(P0.05),在0.33g/kg体重/日、1g/kg体重/日剂量组可明显增强小鼠NK细胞活性(P0.01),1g/kg体重/日剂量组能显著提高小鼠的单核-巨噬细胞吞噬功能(P0.01)。结论沙棘油具有抑制小鼠S-180肿瘤的作用、明显增强小鼠NK细胞活性、能显著提高小鼠的单核-巨噬细胞吞噬功能。     

Lipopolysaccharide enhances bactericidal activity in Dictyostelium discoideum cells

Innate immune cells respond to invading microbes upon detection of pathogen-associated molecular patterns (PAMPS). PAMP-recognition machinery is evolutionarily conserved, allowing for characterization in model organisms. The model organism Dictyostelium discoideum can exist as single-celled amoebae, which phagocytize bacteria for nutrients. Although D. discoideum is used extensively to study phagocytosis, it has not been determined if D. discoideum detects bacterial PAMPs using pattern-recognition machinery. Here we show that D. discoideum mounts responses against the bacterial cell wall PAMP, lipopolysaccharide (LPS). Upon treatment with LPS or its active component Lipid A, D. discoideum cells more efficiently clear phagocytized bacteria. LPS-enhanced bactericidal activity appears dependent both on MAPK signaling pathways as well as on the D. discoideum toll/interleukin-1 receptor domain-containing protein, TirA. These findings indicate that pattern-recognition machinery required to detect and respond to bacterial PAMPs may be conserved in D. discoideum.     

Hydrogen peroxide is produced by E. coli challenged haemocytes and regulates phagocytosis, in the medfly Ceratitis capitata. The active role of superoxide dismutase

Hydrogen peroxide (H₂O₂) participates as a second messenger in cell signaling. In this paper, the role of H₂O₂ was investigated, in Escherichia coli phagocytosis by the haemocytes of the medfly Ceratitis capitata. Block of H₂O₂ synthesis by specific enzymic inhibitors, namely N-ethylmaleimide (NEM) for NADPH oxidase and diethyldithiocarbamate (DDC) for SOD, resulted in the increase of E. coli phagocytosis. Immunoblot analysis, flow cytometry and confocal microscopy, revealed the constitutive expression of SOD, in the medfly haemocytes. Phagocytosis increased by small interfering RNA (siRNA) for SOD, revealing the active involvement of SOD and H₂O₂. Immunoblot analysis showed an increase of the ERK1/2 phosphorylation, in the presence of the above H₂O₂ synthesis enzymic inhibitors. In addition, confocal microscopy showed no co-localization of SOD with β integrin subunit. It appears that SOD participates in the regulation of bacterial phagocytosis, due to involvement of the produced H₂O₂ in the differential phosphorylation of MAP kinases.     

小胶质细胞体外吞噬模型的建立及相关炎症因子的研究

目的: 建立以细胞凋亡信号－磷脂酰丝氨酸(PS)介导的小胶质细胞体外吞噬模型,研究小胶质细胞发挥吞噬功能时炎症因子的表达变化。方法: 用N-乙基马来酰胺(NEM)预处理红细胞,随后整合氧化PS,制备含氧化PS信号的红细胞凋亡模型,并测定小胶质细胞对整合氧化PS信号红细胞吞噬率的变化。同时, real-time PCR检测小胶质细胞中炎症因子白细胞介素1β(IL-1β)和肿瘤坏死因子(TNF-α)的表达情况,研究小胶质细胞吞噬功能与炎症功能之间的关系。结果: 小胶质细胞对整合氧化PS红细胞的吞噬率显著高于对照组(P<0.01),同时炎症因子IL-1β和TNF-α的mRNA表达水平明显减少。结论: 成功制备小胶质细胞体外吞噬凋亡细胞模型,小胶质细胞的吞噬作用可能是自身炎症因子IL-1β和TNF-α在转录水平上降低的诱因。     

吞噬细胞杀菌功能试验检测转移因子的免疫活性

目的以吞噬细胞杀菌功能试验替代吞噬功能试验,检测转移因子的免疫活性。方法MTT法和手工计数法分别检测小鼠吞噬细胞杀菌功能和吞噬功能,直线回归分析两者相关性。结果TF组小鼠吞噬细胞杀菌率和吞噬率均分别高于NS组、空白组（P〈0.05）,各组杀菌率与吞噬率具有较好的相关关系（r〉0.8）。结论MTT法检测吞噬细胞杀菌功能试验是一种简便、经济、准确、客观的方法,可以替代吞噬功能试验用以转移因子非特异性免疫活性的检测。     

The hepatic sinusoidal endothelial lining and colorectal liver metastases

Colorectal cancer （CRC） is a common malignant disease and the severe nature of cases in men and women who develop colorectal cancer makes this an important socio-economic health issue. Major challenges such as understanding and modeling colorectal cancer pathways rely on our understanding of simple models such as outlined in this paper. We discuss that the development of novel standardized approaches of multidimensional （correlative） biomolecular microscopy methods facilitates the collection of （sub） cellular tissue information in the early onset of colorectal liver metastasis and that this approach will be crucial in designing new effective strategies for CRC treatment. The application of X-ray micro-computed tomography and its potential in correlative imaging of the liver vasculature will be discussed.     

Dendritic cells in human aging

Dendritic cells (DCs) play a critical role in linking innate and adaptive immunity. A role of DCs in immunosenescence and chronic inflammation associated with aging has not been investigated in detail. In this article, we will briefly review DCs biology and changes associated with human aging.     

Phagocytosis mediates specificity in the immune defence of an invertebrate, the woodlouse Porcellio scaber (Crustacea: Isopoda)

Specificity and memory are the hallmarks of the adaptive immune system of vertebrates. However, phenomena of specificity upon priming of immunity have recently been demonstrated also in invertebrates, which rely exclusively on innate immune defence. It has been suggested that phagocytosis might represent a core candidate for such specificity in invertebrates. We here developed in vitro phagocytosis measurements for different bacteria in the woodlouse Porcellio scaber (Crustacea: Isopoda). After immune priming with heat-killed bacteria, hemocytes showed increased phagocytosis of a previously encountered bacterial strain compared to other bacteria. These data support the role of phagocytosis in invertebrate immunological specificity and suggest a high degree of specificity that even enables to differentiate between strains of the same bacterial species.