Biomedical subjects

T J Gross

Publications and source records attributed to T J Gross.

22 records · Page 2Linked to original sources

PubMed1991

Noninfectious pulmonary diseases masquerading as community-acquired pneumonia.

A wide spectrum of pulmonary disorders may manifest clinical and radiographic features consistent with infectious pneumonitis. Bronchiolitis obliterans, eosinophilic pneumonia, hypersensitivity pneumonitis, pulmonary vasculitis, alveolar hemorrhage, and alveolar proteinosis all may be difficult to distinguish from community-acquired pneumonia. The salient clinical features of these disorders are reviewed in this article. In addition, specific diagnostic and therapeutic approaches that may aid in differentiating these unusual diseases from the pulmonary infections they mimic are outlined.

Acute Disease↗

PubMed1990

The THP-1 cell line is a urokinase-secreting mononuclear phagocyte with a novel defect in the production of plasminogen activator inhibitor-2.

Mononuclear phagocytes regulate the generation of plasmin by secreting urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-2 (PAI-2). We investigated the production of plasminogen activator (PA) and PA inhibitor by the human monocytic leukemia cell line, THP-1. Similar to U937 monoblast-like cells and peripheral blood monocytes (PBM), THP-1 cells produce a PA that is specifically neutralized by anti-uPA antibody and comigrates with human high molecular mass uPA (54 kDa) on casein-plasminogen zymogaphy. PA activity could be dissociated from intact THP-1 cells by brief treatment with a weak acid-glycine buffer, indicating that the uPA is secreted and bound to receptors on the plasma membrane. Regulation of uPA proceeds normally in THP-1 cells, with cell-associated PA activity increasing from 77 +/- 20 to 163 +/- 26 and 325 +/- 30 mPU/10(6) cells in response to PMA and LPS, respectively; parallel increases in steady state levels of uPA mRNA were observed. In contrast to normal expression of uPA activity, functional PAI-2 could not be demonstrated in either the conditioned media or cell lysates of THP-1 under basal or stimulated conditions. Both U937 and PBM secrete low levels of PA inhibitor activity that increase substantially in response to stimulation with PMA and LPS. Immunoreactive PAI-2, measured by ELISA, was undetectable in THP-1 lysates or conditioned medium, but was consistently present in U937 and PBM, paralleling the presence of PA inhibitor activity. THP-1 cells express low levels of an abnormally sized mRNA for PAI-2 and demonstrate a regulatory defect whereby steady state levels of PAI-2 mRNA are markedly reduced upon stimulation with PMA or LPS. By contrast, U937 and PBM respond to identical stimulation with increases in PAI-2 mRNA. We conclude that THP-1 cells express a structurally abnormal species of PAI-2 mRNA, with complete loss of inhibitory activity as well as altered function of PMA- and LPS-responsive regulatory elements.

Blotting, Northern↗

PubMed1990

Expression of urokinase-type plasminogen activator by rat pulmonary alveolar epithelial cells.

Intra-alveolar fibrin deposition accompanies many forms of inflammatory lung injury. Appropriate clearance of this fibrin matrix is important for normal healing and remodeling. The local generation of plasmin by the action of plasminogen activators (PAs) represents a pivotal step in the fibrinolytic process. To investigate whether the alveolar epithelium plays a role in the modulation of intra-alveolar fibrinolysis, we have studied PA regulation by rat pulmonary alveolar epithelial cells. We have found large quantities of PA activity both in conditioned media and cell lysates from epithelial monolayers in culture. Casein-plasminogen zymography reveals that this PA activity migrates as a tight doublet with an apparent mol wt of 45 kD, clearly distinct from rat tissue-type PA (tPA, greater than 68 kD). Analysis of freshly isolated type II alveolar epithelial cells demonstrates readily measurable PA activity in cell lysates, as well as expression of urokinase-type PA (uPA) mRNA on Northern blot analysis. Upregulation of PA activity occurs progressively with time in culture as the alveolar epithelial cells lose type II cell characteristics and become more flattened. Stimulation of alveolar epithelial cell monolayers with lipopolysaccharide or tumor necrosis factor increases levels of secreted PA activity. The relative abundance of uPA mRNA was shown to change in parallel with PA activity during in vitro differentiation or after exposure to inflammatory mediators. Thus, alveolar epithelial cells are likely an important source of uPA in the lung, the expression of which is influenced by the state of cellular differentiation as well as the presence of inflammatory mediators.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Expression of xanthine oxidase activity by murine leukocytes.

The enzyme xanthine oxidase participates in the pathogenesis of tissue ischemia-reperfusion injury by depleting purine pools and generating toxic oxygen metabolites. The role of xanthine oxidase in inflammatory cell populations has not been defined. We examined the level of xanthine oxidase activity expressed by murine leukocytes both in the resting state, and after in vivo and in vitro exposure to inflammatory stimuli. The contribution of xanthine oxidase to inflammation may vary among tissue compartments, so leukocytes harvested from several tissues were studied. Resident murine peritoneal macrophages consistently expressed xanthine oxidase activity (291 +/- 55 microIU/10(6) cells). Thioglycolate-elicited peritoneal macrophages contained similar levels of xanthine oxidase activity (265 +/- 42 microIU/10(6) cells). By contrast, resident murine alveolar macrophages expressed one tenth the xanthine oxidase activity (24 +/- 4 microIU/10(6) cells). Xanthine oxidase activity was also consistently found in murine peritoneal neutrophils (127 +/- 28 microIU/10(6) cells) but not in splenic lymphocytes. In vitro studies were performed to determine whether xanthine oxidase activity of resident peritoneal macrophages could be modulated by exogenous stimuli relevant to the pathogenesis of inflammation. Lipopolysaccharide caused a 62% +/- 9% reduction in cellular xanthine oxidase activity (p less than 0.02). Interferon-gamma alone had no effect on xanthine oxidase activity; however, interferon-gamma and lipopolysaccharide together caused a striking reduction in cellular xanthine oxidase activity, reaching 25% +/- 2% of unstimulated control cells (p less than 0.001). We conclude that murine macrophages and neutrophils are potentially important sources of xanthine oxidase activity in inflamed tissues. In addition, the activity of xanthine oxidase in macrophages is tissue specific and is modulated in vitro by proinflammatory stimuli.

Animals↗