Biomedical subjects

Ulrich Baumann

Publications and source records attributed to Ulrich Baumann.

41 records · Page 3Linked to original sources

PubMed2003

New insights into the pathophysiology and in vivo function of IgG Fc receptors through gene deletion studies.

Fc-receptors for IgG (FcyRs) are critically involved at multiple stages of an immune response, ranging from antigen presentation and regulation of antibody production to the end-stage effector mechanisms of inflammation. IgG autoantibodies that are detectable in the majority of autoimmune diseases are ligands for FcgammaRs. The three classes, FcgammaRI, FcgammaRII, and FcgammaRIII, vary in their antibody affinity, cellular expression and in vivo function. We review the current knowledge on the regulation and diverse functions of the distinct FcgammaRs and describe the evidence of their important immunoregulatory roles in autoimmunity based on recent work in animal models.

Animals↗

PubMed2002

A structural basis for the activity of retro-Diels-Alder catalytic antibodies: evidence for a catalytic aromatic residue.

The nitroxyl synthase catalytic antibodies 10F11, 9D9, and 27C5 catalyze the release of nitroxyl from a bicyclic pro-drug by accelerating a retro-Diels-Alder reaction. The Fabs (antigen-binding fragments) of these three catalytic antibodies were cloned and sequenced. Fab 9D9 was crystallized in the apo-form and in complex with one transition state analogue of the reaction. Crystal structures of Fab 10F11 in complex with ligands mimicking substrate, transition state, and product have been determined at resolutions ranging from 1.8 to 2.3 A. Antibodies 9D9 and 10F11 show increased shape complementarity (as quantified by the program sc) to the hapten and to a modeled transition state as compared with substrate and product. The shape complementarity is mediated to a large extent by an aromatic residue (tyrosine or tryptophan) at the bottom of the hydrophobic active pocket, which undergoes pi-stacking interactions with the aromatic rings of the ligands. Another factor contributing to the different reactivity of the regioisomers probably arises because of hydrogen-bonding interactions between the nitroxyl bridge and the backbone amide of PheH101 and possibly a conserved water molecule.

Amino Acid Sequence↗

PubMed2002

Crystal structure of the human supernatant protein factor.

Supernatant protein factor (SPF) promotes the epoxidation of squalene catalyzed by microsomes. Several studies suggest its in vivo role in the cholesterol biosynthetic pathway by a yet unknown mechanism. SPF belongs to a family of lipid binding proteins called CRAL_TRIO, which include yeast phosphatidylinositol transfer protein Sec14 and tocopherol transfer protein TTP. The crystal structure of human SPF at a resolution of 1.9 A reveals a two domain topology. The N-terminal 275 residues form a Sec14-like domain, while the C-terminal 115 residues consist of an eight-stranded jelly-roll barrel similar to that found in many viral protein structures. The ligand binding cavity has a peculiar horseshoe-like shape. Contrary to the Sec14 crystal structure, the lipid-exchange loop is in a closed conformation, suggesting a mechanism for lipid exchange.

Carrier Proteins↗

PubMed2002

C5a anaphylatoxin is a major regulator of activating versus inhibitory FcgammaRs in immune complex-induced lung disease.

IgG Fc receptors (FcgammaRs, especially FcgammaRIII) and complement (in particular, C5a anaphylatoxin) are critical effectors of the acute inflammatory response to immune complexes (ICs). However, it is unknown whether and how these two key components can interact with each other in vivo. We use here a mouse model of the acute pulmonary IC hypersensitivity reaction to analyze their potential interaction. FcgammaRIII and C5aR are coexpressed on alveolar macrophages (AMs), and both FcgammaRIII and C5aR mutant mice display impaired immune responses. We find that recombinant human C5a (rhC5a) can control inverse expression of various FcgammaRs, and costimulation of ICs with rhC5a results in strong enhancement of FcgammaRIII-triggered cellular activation in vitro and in vivo. Moreover, we show here that early IC-induced bioactive C5a, and its interaction with C5aR, causes induction of activating FcgammaRIII and suppression of inhibitory FcgammaRII on AMs that appears crucial for efficient cytokine production and neutrophil recruitment in lung pathology. Therefore, C5a, which is a potent chemoattractant, has a broader critical function in regulating the inhibitory/activating FcgammaRII/III receptor pair to connect complement and FcgammaR effector pathways in immune inflammation.

Animals↗

PubMedDate not supplied

Additive effect of dornase alfa and Nacystelyn on transportability and viscoelasticity of cystic fibrosis sputum.

OBJECTIVE: To investigate the effect of dornase alfa (DA), Nacystelyn (NAL) and their combination on mucociliary transportability and mucus viscoelasticity of cystic fibrosis (CF) sputum, and to assess whether the combination possesses an additive effect. DESIGN: Determination of transportability in frog palate and viscoelasticity in vitro. SETTING: Research laboratory at a medical centre. PATIENTS: Sputa from 15 patients with CF, chronically infected with Pseudomonas aeruginosa, were studied. INTERVENTIONS: Sputum samples were incubated without any drug solution as a control, and with normal saline, DA, NAL and a mixture of DA and NAL in concentrations approximating those achieved in clinical practice. RESULTS: Normal saline (10% volume) by itself had a small effect on CF sputum transportability with a mean increase of 9%, and on viscoelasticity with a mean of decrease of 0.22 log units, respectively, compared with control (incubation without saline). DA (200 nM) further increased the transportability by a mean of 35% versus saline and decreased viscoelasticity by a mean of 0.30 log units. NAL (100 M) increased the transportability by a mean of 32% and decreased viscoelasticity by a mean of 0.22 log units from the levels achieved with saline. The mixture of DA plus NAL at one-half of the above concentration of each agent produced an additional increase in the transportability, by a mean of 18%, and a further decrease in viscoelasticity, by a mean of 0.25 log units, compared with DA or NAL as a single treatment. CONCLUSIONS: The combination of DA and NAL exhibits an additive effect for both the viscoelasticity and transportability of CF sputum samples. The two agents appear to act well together in breaking down the bonding due to extracellular DNA and mucins. Clinical studies should be undertaken to see whether the additive combination at lower concentration produces the anticipated benefits of improved airway clearance and fewer side effects.

Acetylcysteine↗