The Role of Arachidonic Acid Metabolites in Mononuclear Phagocytic Cell Interactions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65162/1/j.1365-4362.1986.tb04543.x.pd

Completions of implicitly defined linear time varying vector fields

AbstractThe stabilization of constraints through such techniques as Baumgarte stabilization has been used in the simulation community for some time. This and a number of control problems can be viewed as either extending, or modifying, a vector field off of some manifold. Generally these approaches required the equations to have a special structure. Motivated by numerical simulation there has recently been new progress on doing this stabilization in numerically robust ways for larger classes of systems. In this paper we point out how earlier linear time invariant results do not immediately apply to the linear time varying case and then analyze the linear time varying case

C‐C chemokine‐induced eosinophil chemotaxis during allergic airway inflammation

The production of eosinophil‐specific chemotactic factors during allergic airway responses may be a pivotal event resulting in eosinophil accumulation, activation, and airway damage. Recent studies have identified specific chemokines that may play crucial roles in recruitment of eosinophils to the site of allergic reactions. In this study we have utilized an established model of schistosome egg antigen (SEA)‐mediated allergic responses to examine the role of specific C‐C chemokines [macrophage inflammatory protein‐1α (MIP‐1α), RANTES, and monocyte chemoattractant protein‐1 (MCP‐1)] in eosinophil recruitment. We have previously identified a role for MIP‐1α in eosinophil accumulation in the lung and airway during allergic airway inflammation. We extend those studies using in vitro eosinophil chemotaxis to establish that both MIP‐1α and RANTES are potent eosinophil chemotactic factors in lungs during allergic airway responses. Morphometric analysis demonstrated a peribronchial accumulation of eosinophils within the lungs beginning at 8 h, peaking at 24 h, and plateauing at 48–96 h after allergen (SEA) challenge. Utilizing whole‐lung homogenates from allergen‐challenged mice, in vitro eosinophil chemotactic assays demonstrated significant increases in eosinophil chemotactic activity with 8‐h lung homogenates and peak activity with samples from 24‐h lung homogenates. These data correlated with the morphometric analysis of peribronchial eosinophil accumulation in situ. When lung homogenates from allergen‐challenged mice were preincubated in vitro with antibodies specific for MIP‐1α, RANTES, or MCP‐1, a significant reduction in eosinophil chemotaxis was observed with only MIP‐1α and RANTES neutralization. Altogether, these studies indicate that RANTES and MIP‐1α are major eosinophil chemotactic factors produced during allergic airway responses. J. Leukoc. Biol. 60:573–578; 1996.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141543/1/jlb0573.pd

Arachidonic acid metabolites regulate interleukin-1 production

We have investigated the role of arachidonic acid metabolites in the regulation of interleukin-1 production by murine peritoneal macrophages. Indomethacin a potent inhibitor of prostaglandin synthesis caused a dose-dependent augmentation of lipopolysaccharide induced interleukin production (up to 7-fold at 5 [mu]M). In contrast, lipoxygenase inhibitors, nordihydroguarietic acid and nafazatrom had no effect at doses that did not significantly decrease prostaglandin synthesis. Added to lipopolysaccharide stimulated cultures, PGE2 suppressed interleukin in a dose-dependent manner. Zymosan induced interleukin was also augmented by indomethacin but unlike lipopolysaccharide treated cultures was suppressed by nordihydroguarietic acid. These data suggest that arachidonate metabolites may be potent autoregulators of macrophage interleukin-1 production.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25698/1/0000252.pd

The Three-Dimensional Circumstellar Environment of SN 1987A

We present the detailed construction and analysis of the most complete map to date of the circumstellar environment around SN 1987A, using ground and space-based imaging from the past 16 years. PSF-matched difference-imaging analyses of data from 1988 through 1997 reveal material between 1 and 28 ly from the SN. Careful analyses allows the reconstruction of the probable circumstellar environment, revealing a richly-structured bipolar nebula. An outer, double-lobed ``Peanut,'' which is believed to be the contact discontinuity between red supergiant and main sequence winds, is a prolate shell extending 28 ly along the poles and 11 ly near the equator. Napoleon's Hat, previously believed to be an independent structure, is the waist of this Peanut, which is pinched to a radius of 6 ly. Interior to this is a cylindrical hourglass, 1 ly in radius and 4 ly long, which connects to the Peanut by a thick equatorial disk. The nebulae are inclined 41\degr south and 8\degr east of the line of sight, slightly elliptical in cross section, and marginally offset west of the SN. From the hourglass to the large, bipolar lobes, echo fluxes suggest that the gas density drops from 1--3 cm^{-3} to >0.03 cm^{-3}, while the maximum dust-grain size increases from ~0.2 micron to 2 micron, and the Si:C dust ratio decreases. The nebulae have a total mass of ~1.7 Msun. The geometry of the three rings is studied, suggesting the northern and southern rings are located 1.3 and 1.0 ly from the SN, while the equatorial ring is elliptical (b/a < 0.98), and spatially offset in the same direction as the hourglass.Comment: Accepted for publication in the ApJ Supplements. 38 pages in apjemulate format, with 52 figure

Regularization of linear and nonlinear descriptor systems

Differential-algebraic equations (DAEs) present today the state-of-the-art in dynamical systems arising from automated modularized modeling in almost all areas of science and engineering. While the modeling becomes more and more convenient, the resulting models are typically not easy to treat with current numerical simulation, control and optimization methods. In many cases a reformulation of the models or even a regularization is necessary to avoid failure of the computational methods. In this contribution we will discuss general DAE control problems and how they can be systematically reformulated and regularized so that the resulting system can be used in control and optimization procedures without much further difficulties

Mononuclear Cell Adherence Induces Neutrophil Chemotactic Factor/Interleukin‐8 Gene Expression

The accumulation of polymorphonuclear cells (PMN) in tissue is an essential element of the inflammatory response that is important in host defense. Adherence to endothelium constitutes the first step in PMN migration from the vascular compartment to the interstitium. We demonstrate that human peripheral blood mononuclear cells (PBMC) adherent to plastic can result in expression of interleukin‐8 (IL‐8), a potent PMN chemoattractant and activating cytokine. Northern blot analyses showed PBMC adherent to plastic expressed IL‐8 steady‐state mRNA levels by 30 min, peaked at 8 h, and then decreased over the next 16 h. In contrast, nonadherent PBMC (cultured in teflon chambers) expressed less than 25% of the maximal IL‐8 steady‐state mRNA levels as compared with adherent PBMC. Adherent PBMC‐associated IL‐8 determined by immunohistochemistry, supernatant chemotactic bioactivity, and extracellular antigenic IL‐8 paralleled IL‐8 mRNA expression. Antigenic and bioactive IL‐8 were significantly apparent by 4–8 h, respectively, and increased significantly to maximal levels by 24 h. Furthermore, adherent PBMC IL‐8 gene expression was suppressed by either concomitant treatment with actinomycin‐D or cycloheximide, yet specific neutralizing antibodies directed against either IL‐1β or tumor necrosis factor (TNF)‐α failed to alter adherence‐induced steady‐state IL‐8 mRNA levels. These data support the hypothesis that PBMC adherence is an important signal for the production of IL‐8, and may be essential to the development of the inflammatory response through the elicrtation of PMN.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141636/1/jlb0287.pd

Mast cells produce ENA‐78, which can function as a potent neutrophil chemoattractant during allergic airway inflammation

The inflammatory response during allergic airway inflammation involves the recruitment of multiple leukocyte populations, including neutrophils, monocytes, lymphocytes, and eosinophils. All of these populations likely contribute to the pathology observed during repeated episodes of allergic airway inflammation. We have examined the role of a human neutrophil‐specific chemokine (C‐x‐C), ENA‐78, in a model of allergic airway responses and identified murine mast cells as a cellular source of an ENA‐78‐like molecule. Within this allergic airway model, neutrophil infiltration into the airway occurs within 4–8 h post‐allergen challenge, persists within the airway until 24 h, and resolves by 48 h post‐challenge. Neutrophil influx precedes the eosinophil infiltration, which peaks in the airway at 48 h post‐allergen challenge. In this study the production of ENA‐78 from challenged lungs demonstrated a significant increase in the allergen‐,but not vehicle‐, challenged lungs. In vivo neutralization of ENA‐78 by passive immunization demonstrated a significant decrease in peak neutrophil infiltration at 8 h, with no effect on the eosinophil infiltration at 48 h post‐challenge. Because ENA‐78 has been shown to be chemotactic for neutrophils and given the involvement of mast cell degranulation in allergic responses, we examined mast cells for the presence of ENA‐78. Cultured mast cells spontaneously released ENA‐78, but on activation with IgE + antigen, NG‐L‐arginine methyl ester or compound 48/80 produced significantly increased levels of ENA‐78. Supernatants from sonicated MC‐9 mast cells induced an overwhelming influx of neutrophils into the BAL by 4 h post‐intratracheal injection into mice, suggesting that the mast cell is a significant source of neutrophil chemotactic factors. Mast cell supernatant‐mediated neutrophil infiltration was substantially decreased by preincubation of the supernatant with antibodies specific for ENA‐78. These data indicate a major neutrophil chemotactic protein produced by mast cells during allergic responses may be mast cell‐derived ENA‐78. J. Leukoc. Biol. 63: 746–751; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141710/1/jlb0746.pd

Dynamics of Arachidonic Acid Metabolism in Macrophages From Delayed‐Type Hypersensitivity (Schistosoma mansoni egg) and Foreign‐Body‐Type Granulomas

The present study examines the kinetics of arachidonic acid (AA) metabolism by murine macrophages isolated from sites of experimentally induced pulmonary granulomatous inflammation. Macrophages of T‐cell‐mediated hypersensitivity lesions induced by Schistosoma mansoni eggs (SE‐GM) and non‐T‐cell‐mediated foreign‐body‐type lesions (FB‐GM) induced by Sephadex beads were examined. Overall, macrophages from both types of lesions produced mainly lipoxygenase pathway metabolites, leukotrienes, and monohydroxyeicosatetraenoic acids (mono‐HETEs). Early after induction (4 days [4D]), SE‐GM showed an augmented zymosan‐stimulated AA release and metabolism compared to resident peritoneal macrophages. Macrophages from mature lesions (8–32D) showed constitutive synthesis of metabolites and were refractory to zymosan stimulation. Both SE‐GM and FB‐GM showed augmented AA uptake incorporating a large proportion into neutral lipids. A direct comparison of SE‐GM and FB‐GM revealed that the T‐cell‐mediated lesion produced lesser amounts of prostaglandins and leukotrienes and showed reduced incorporation of AA into phosphatidylcholine. These data suggest that AA metabolism by granuloma macrophages is sequentially modified during recruitment and activation at sites of chronic inflammation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141165/1/jlb0671.pd

A New View of the Circumstellar Environment of SN 1987A

We summarize the analysis of a uniform set of both previously-known and newly-discovered scattered-light echoes, detected within 30" of SN 1987A in ten years of optical imaging, and with which we have constructed the most complete three-dimensional model of the progenitor's circumstellar environment. Surrounding the SN is a richly-structured bipolar nebula. An outer, double-lobed ``peanut,'' which we believe is the contact discontinuity between the red supergiant and main sequence winds, is a prolate shell extending 28 ly along the poles and 11 ly near the equator. Napoleon's Hat, previously believed to be an independent structure, is the waist of this peanut, which is pinched to a radius of 6 ly. Interior, the innermost circumstellar material lies along a cylindrical hourglass, 1 ly in radius and 4 ly long, which connects to the peanut by a thick equatorial disk. The nebulae are inclined 41o south and 8o east of the line of sight, slightly elliptical in cross section, and marginally offset west of the SN. The 3-D geometry of the three circumstellar rings is studied, suggesting the equatorial ring is elliptical (b/a<0.98), and spatially offset in the same direction as the hourglass. Dust-scattering models suggest that between the hourglass and bipolar lobes: the gas density drops from 1--3 cm^{-3} to >0.03 cm^{-3}; the maximum dust-grain size increases from ~0.2 micron to 2 micron; and the Si:C dust ratio decreases. The nebulae have a total mass of ~1.7 Msun, yielding a red-supergiant mass loss around 5*10^{-6} Msun yr^{-1}.Comment: Accepted for publication in ApJ 2/14/05. 16 pages in emualteapj forma