Innate recognition of bacteria: engagement of multiple receptors

Until recently, consensus was that the mechanism of action of the innate immune system was a simplified one. Current research findings in the field of innate recognition of bacteria suggest that it involves complex associations of receptors depending on cell type and bacterial stimuli, CD14, integrins, Toll-like receptors (TLRs), CD55, ion channels, and activation clusters containing heat shock proteins, chemokine receptor 4 and a plethora of other molecules have been shown to serve as key molecules in bacterial recognition. In this article, we review all the advances in the field and discuss the possibility that the repertoire for recognition of pathogens is defined by the combinational engagement of multiple receptors.     

The influence of surface roughness of titanium on beta1- and beta3-integrin adhesion and the organization of fibronectin in human osteoblastic cells

Mechanisms of cell adhesion and extracellular matrix formation are primary processes in the interaction with the material surface of an implant which are controlled by integrin receptors. The aim of our study was to find out whether beta1- and beta3-integrins of osteoblastic cells sense the surface topography of titanium, and if structural alterations of integrin adhesions were involved in the organization of fibronectin. Pure titanium surfaces were modified by polishing (P), machining (NT), blasting with glass spheres (GB), and blasting with corundum particles (CB) resulting in increasing roughness. Confocal microscopic investigations revealed fibrillar adhesions of beta1- and alpha5-integrins on P, NT, and GB, but on CB with its sharp edges these integrin subunits did not form fibrillar adhesions. beta3 generally appeared in focal adhesions. We observed aligned fibrillar structures of fibronectin on NT not only on the basal site but interestingly, also on the apical cell surface. In contrast, on CB, fibronectin appeared apically clustered. We suggest that this alignment of fibronectin fibrils depends on the directed actin cytoskeleton and in particular, on the capability of the beta1-integrins to form fibrillar adhesions, which is affected by the surface roughness of titanium.     

Detecting danger--or just another odorant? Olfactory sensitivity for the fox odor component 2,4,5-trimethylthiazoline in four species of mammals

2,4,5-trimethylthiazoline (TMT) is a volatile component of the anal gland secretion of the red fox and elicits behavioral and physiological fear responses in the rat. Using instrumental conditioning paradigms, we determined olfactory detection thresholds for TMT in three rats, a natural prey species of the red fox, and compared their performance to that of three squirrel monkeys, three spider monkeys and four pigtail macaques, all non-prey species of the red fox. We found that the rats were able to discriminate concentrations between 0.04 and 0.10 ppt (parts per trillion) of TMT from the odorless solvent which is by far the lowest olfactory detection threshold for an odorant reported in rats so far. In contrast, the spider monkeys needed 0.14-1.38 ppb (parts per billion), the pigtail macaques 0.41-4.07 ppb, and the squirrel monkeys 4.07-13.80 ppb to detect TMT which does not rank among the lowest olfactory thresholds reported for these three primate species. Thus, these results support the assumption that the behavioral relevance of an odorant may be an important determinant of a species' olfactory sensitivity.     

Stimulation of DNA synthesis in mouse lymphoid cells by polyanions in vitro. I. Target cells and possible mode of action

The effect of dextran sulfate on [³H]dThd incorporation in lymphoid cells was investigated. The polyanion activated DNA synthesis in spleen and bone marrow cells of normal mice. The highest rate of activation was detected in spleen cells of athymic (nude) mice; the ratio of [³H]dThd incorporation was higher in TxBM spleen cells of thymectomized, lethally irradiated and bone marrow protected mice than in spleen cells of normal donors. Thymus cells of normal mice could not be stimulated, but a slight response was obtained in cortisone-resistant thymus cells. A synergetic effect was found in normal thymus cells using a combination of dextran sulfate and phytohemagglutinin (PHA). In contrast, lipopolysaccharide and PHA showed no synergetic effect. The possible mode of action of polyanions as de-repressors of DNA synthesis is discussed.     

Über funktionelle Unterschiede zwischen Dünn-und Dickdarm—dargestellt an den verschiedenen Reaktionen der Darmschleimhaut bei Angebot von Lösungen nicht penetrabler Solute und steigender Osmolarität

Zusammenfassung Bei Instillation von Mannitlösungen steigender Osmolarität in durchblutete, in situ belassene Jejunum- und Colonschlingen von Ratten reagieren beide Darmabschnitte unterschiedlich.Während die durch Enterosorption binnen 30 min in das Jejunum gelangte Flüssigkeitsmenge 250% des Instillats ausmacht, beträgt der analoge Wert beim Colon nur 100%. Die enterosorbierten Mengen an Na⁺, Cl^– und Urea sind im Jejunum wesentlich größer als im Colon, da nicht nur die enterosorbierte Flüssigkeitsmenge größer ist, sondern weil auch die intraintestinalen Konzentrationen höher liegen.Zwischen den Ca⁺⁺-Konzentrationen im Jejunum und Colon bestehen keine Unterschiede, die K⁺-Konzentration ist im Colon höher. Bei Berücksichtigung der Wasserbewegungen ist die enterosorbierte Ca⁺⁺-Menge im Jejunum, die K⁺-Menge dagegen im Colon größer.Während der Versuchszeit — 30 min — erfolgt im Jejunum ein osmolarer Konzentrationsausgleich aller Lösungen mit dem Plasma, deren Konzentration kleiner als die 1,66 fache Blutisotonie ist. Im Colon stellt sich dieser Ausgleich auch für eine Lösung von 1,33 facher Blutisotonie nicht mehr ein.Die Colonschleimhaut verhält sich demnach so, als ob hier die Exsorption von Wasser, Na⁺, Cl^–, Ca⁺⁺ und Urea wesentlich stärker behindert wäre als die durch die Schleimhaut des Jejunums.Instillation großer Volumina stark hypertoner (ca. 2000 mOsmol/l) Lösungen, deren Solute nur schwer absorbiert werden können, führen zu einem so großen Einstrom von Blut- und Körperflüssigkeit in den Intestinaltrakt, daß Ratten in schwerer Exsiccose sterben. Dabei steigt der Anteil von Zellen am Blutvolumen von 48% auf 68% der Wassergehalt der geprüften Gewebe — quergestreifte und Herzmuskulatur, Gehirn — sinkt ab.     

Microscopic polyangiitis (microscopic polyarteritis)

Microscopic polyangiitis ("microscopic polyarteritis") is a form of necrotizing small vessel vasculitis that most often affects venules, capillaries, arterioles, and small arteries, although it occasionally involves medium-sized arteries. Microscopic polyangiitis is a more appropriate name than microscopic polyarteritis because some patients have no evidence for arterial involvement. The absence or paucity of immunoglobulin localization in vessel walls distinguishes microscopic polyangiitis from immune complex mediated small vessel vasculitis, such as Henoch-Schonlein purpura and cryoglobulinemic vasculitis. Clinical, epidemiological, and pathologic differences warrant the separation of microscopic polyangiitis from polyarteritis nodosa on the basis of involvement of capillaries and venules by the former but not the latter. Pauci-immune necrotizing and crescentic glomerulonephritis, and hemorrhagic pulmonary capillaritis are common in patients with microscopic polyangiitis. Microscopic polyangiitis is the most common cause for pulmonary-renal vasculitic syndrome. The vasculitis in patients with microscopic polyangiitis is pathologically indistinguishable from the vasculitis of Wegener's granulomatosis and Churg-Strauss syndrome. Granulomatous inflammation distinguishes Wegener's granulomatosis from microscopic polyangiitis. Asthma and eosinophilia distinguish Churg-Strauss syndrome from microscopic polyangiitis. Microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome are all associated with circulating antineutrophil cytoplasmic autoantibodies.     

Role of radiation therapy in small cell lung cancer: a bio-clinico-pathological review and perspective

The role of radiotherapy in small cell carcinoma of the lung is unsettled; however, the radiosensitivity of this neoplasm is unquestioned. The ability of radiotherapy to cure or improve patients with this disease is still undergoing study. A review of this challenging subject is presented.     

Direct ultrastructural evidence of target-directed polarization by cytotoxic lymphocytes in lesions of human graft-vs-host disease

Cytotoxic lymphocytes are thought to kill target cells by means of potent cytotoxic granules that congregate near the microtubular organizing center and the Golgi apparatus at one pole of the killer cell. We searched for evidence of this type of polarization in 12 lip biopsy specimens from patients with acute and/or chronic graft-vs-host disease (GVHD) compared with two lip specimens from normal individuals. Lymphocytes with such polarization were found in contact with epithelial cells of the squamous mucosa in all 12 cases of GVHD, and cells of the cuboidal minor salivary duct epithelium were found in two of 11 evaluable cases. The data add support to the hypothesis that cytolytic lymphocytes attack epithelial cells in GVHD.