Richard Bucala

Bio: Richard Bucala is an academic researcher from Yale University. The author has contributed to research in topics: Macrophage migration inhibitory factor & Cytokine. The author has an hindex of 119, co-authored 595 publications receiving 54607 citations. Previous affiliations of Richard Bucala include École Polytechnique Fédérale de Lausanne & Rockefeller University.

Regulated Production of Type I Collagen and Inflammatory Cytokines by Peripheral Blood Fibrocytes

Abstract: We recently described a novel population of blood-borne cells, termed fibrocytes, that display a distinct cell surface phenotype (collagen + /CD13 + /CD34 + /CD45 + ), rapidly enter sites of tissue injury, and contribute to scar formation. To further characterize the role of these cells in vivo, we examined the expression of type I collagen and cytokine mRNAs by cells isolated from wound chambers implanted into mice. Five days after chamber implantation, CD34 + fibrocytes but not CD14 + monocytes or CD90 + T cells expressed mRNA for type I collagen. Fibrocytes purified from wound chambers also were found to express mRNA for IL-1β, IL-10, TNF-α, JE/MCP, MIP-1α, MIP-1β, MIP-2, PDGF-A, TGF-β1, and M-CSF. The addition of IL-1β (1–100 ng/ml), a critical mediator in wound healing, to fibrocytes isolated from human peripheral blood induced the secretion of chemokines (MIP-1α, MIP-1β, MCP-1, IL-8, and GROα), hemopoietic growth factors (IL-6, IL-10, and macrophage-CSF), and the fibrogenic cytokine TNF-α. By contrast, IL-1β decreased the constitutive secretion of type I collagen as measured by ELISA. Additional evidence for a role for fibrocytes in collagen production in vivo was obtained in studies of livers obtained from Schistosoma japonicum -infected mice. Mouse fibrocytes localized to areas of granuloma formation and connective matrix deposition. We conclude that fibrocytes are an important source of cytokines and type I collagen during both the inflammatory and the repair phase of the wound healing response. Furthermore, IL-1β may act on fibrocytes to effect a phenotypic transition between a repair/remodeling and a proinflammatory mode.

A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis

Abstract: The macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine and regulates the anti-inflammator effects of glucocorticoids. An important role for MIF within the cytokine cascade is to act in concert with endogenous glucocorticoids to control the set-point and magnitude of the inflammatory response. Elevated expression of MIF in the circulation and in the synovial joint has been documented in rheumatoid arthritis. MIF also has been linked to the development of joint damage and disease pathology in experimental animal models. We describe herein a novel CATT-tetranucleotide repeat polymorphism at position −794 of the human Mif gene and show that it functionally affects the activity of the MIF promoter in gene reporter assays. We describe four genotypes which comprise 5, 6, 7, or 8-CATT repeat units and show that the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients.

The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ

Abstract: Recent studies have identified a novel population of blood-borne cells, termed fibrocytes, that have a distinct cell surface phenotype (collagen+/CD13(+)/CD34(+)/CD45(+)), rapidly enter sites of tissue injury, and synthesize connective tissue matrix molecules. We found by flow cytometry that purified human fibrocytes express each of the known surface components that are required for antigen presentation, including class II major histocompatability complex molecules (HLA-DP, -DQ, and -DR), the costimulatory molecules CD80 and CD86, and the adhesion molecules CD11a, CD54, and CD58. Human fibrocytes induced antigen-presenting cell-dependent T cell proliferation when cultured with specific antigen and this proliferative activity was significantly higher than that induced by monocytes and nearly as high as that induced by purified dendritic cells. Mouse fibrocytes also were found to express the surface components required for antigen presentation and to function as potent APCs in vitro. Mouse fibrocytes pulsed in vitro with the HIV-proteins p24 or gp120 and delivered to a site of cutaneous injury were found to migrate to proximal lymph nodes and to specifically prime naive T cells. These data suggest that fibrocytes play an early and important role in the initiation of antigen-specific immunity.

Fibrocytes: emerging effector cells in chronic inflammation

Abstract: Fibrocytes are mesenchymal cells that arise from monocyte precursors. They are present in injured organs and have both the inflammatory features of macrophages and the tissue remodelling properties of fibroblasts. Chronic inflammatory stimuli mediate the differentiation, trafficking and accumulation of these cells in fibrosing conditions associated with autoimmunity, cardiovascular disease and asthma. This Opinion article discusses the immunological mediators controlling fibrocyte differentiation and recruitment, describes the association of fibrocytes with chronic inflammatory diseases and compares the potential roles of fibrocytes in these disorders with those of macrophages and fibroblasts. It is hoped that this information prompts new opportunities for the study of these unique cells.

The immunoregulatory mediator macrophage migration inhibitory factor (MIF) catalyzes a tautomerization reaction.

Abstract: Recent studies of melanin biosynthesis have uncovered an unusual enzymatic activity which converts the non-naturally occurring D-isomer of 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome) into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). The aim of the present investigation was to isolate and characterize the enzyme catalyzing this tautomerization reaction. After we performed a tissue survey of D-dopachrome tautomerase activity, 10 bovine lenses were homogenized and used as a source of enzyme. A soluble fraction was obtained by high-speed centrifugation and subjected to successive FPLC chromatography on Phenyl-sepharose, Mono S cation-exchange, and Superdex gel-filtration. The isolated enzyme was electrophoresed, blotted onto PVDF membrane, and the N terminus analyzed by gas phase micro-sequencing. The protein catalyzing the conversion of D-dopachrome to DHICA was purified to homogeneity in 14% yield and showed a molecular weight of 12 kD when analyzed by SDS-PAGE. The first 27 amino acid residues of this protein were sequenced and found to be identical with those of bovine macrophage migration inhibitory factor (MIF). The catalytic activity of native MIF was confirmed by studies of purified recombinant human MIF, which showed the same tautomerase activity. While L-dopachrome was not a substrate for this reaction, the methyl esters of the L- and D-isomers were found to be better substrates for MIF than D-dopachrome. MIF has been described recently to be an anterior pituitary hormone and to be released from immune cells stimulated by low concentrations of glucocorticoids. Once secreted, MIF acts to control, or counter-regulate, the immunosuppressive effects of glucocorticoids on the immune system. Although the tested substrate, D-dopachrome, does not occur naturally, the observation that MIF has tautomerase activity suggests that MIF may mediate its biological effects by an enzymatic reaction. These data also offer a potential approach for the design of small molecule pharmacological inhibitors of MIF that may modulate its potent immunoregulatory effects in vivo.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

Multilineage Potential of Adult Human Mesenchymal Stem Cells

Abstract: Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。