Effect of single and multiple inhalation of SDZ OXL 400 on antigen-induced inflammatory cell accumulation into the airways of actively sensitized guinea-pigs

We have analyzed the effect of the soluble guanylate cyclase (sGC) stimulator BAY 41-2272 in a therapeutic intervention in guinea pigs chronically exposed to cigarette smoke (CS). The effects of sGC stimulation on respiratory function, pulmonary hemodynamics, airspace size, vessel remodeling, and inflammatory cell recruitment to the lungs were evaluated in animals that had been exposed to CS for 3 mo. CS exposure was continued for an additional 3 mo in half of the animals and withdrawn in the other half. Animals that stopped CS exposure had slightly lower pulmonary artery pressure (PAP) and right ventricle (RV) hypertrophy than those who continued CS exposure, but they did not recover from the emphysema and the inflammatory cell infiltrate. Conversely, oral BAY 41-2272 administration stopped progression or even reversed the CS-induced emphysema in both current and former smokers, respectively. Furthermore, BAY 41-2272 produced a reduction in the RV hypertrophy, which correlated with a decrease in the PAP values. By contrast, the degree of vessel remodeling induced by CS remained unchanged in the treated animals. Functional network analysis suggested perforin/granzyme pathway downregulation as an action mechanism capable of stopping the progression of emphysema after sGC stimulation. The pathway analysis also showed normalization of the expression of cGMP-dependent serine/kinases. In conclusion, in guinea pigs chronically exposed to CS, sGC stimulation exerts beneficial effects on the lung parenchyma and the pulmonary vasculature, suggesting that sGC stimulators might be a potential alternative for chronic obstructive pulmonary disease treatment that deserves further evaluation.

Download Full-text

Attenuation of hyperoxic lung injury by the 21-aminosteroid U-74389G

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.5.1635 ◽

1995 ◽

Vol 78 (5) ◽

pp. 1635-1641 ◽

Cited By ~ 5

Author(s):

S. Tasaka ◽

A. Ishizaka ◽

T. Urano ◽

K. Sayama ◽

F. Sakamaki ◽

...

Keyword(s):

Lung Injury ◽

Lung Tissue ◽

Guinea Pigs ◽

Weight Ratio ◽

Dry Weight ◽

Endothelial Damage ◽

Lung Water ◽

Tissue Samples ◽

Cell Accumulation ◽

Hyperoxic Lung Injury

Hyperoxic lung injury is attributable to oxygen radicals produced under hyperoxic conditions. The 21-aminosteroid (AS), U-74389G, is a potent antioxidant. We examined the effect of U-74389G on lung injury in guinea pigs during exposure to 90% O2 for 48 h. We injected either vehicle or 10 mg/kg of U-74389G 30 min before the O2 exposure and injected the same dose 12, 24, and 36 h later. We performed two series of experiments after exposure. In the first series, we measured the clearance rate of 99mTc-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups consisting of 1) control (n = 6) O2 alone (n = 6), and 3) O2 + AS (n = 6). In the second series, pulmonary endothelial injury was estimated by using 28 guinea pigs divided into four experimental groups consisting of 1) control (n = 8), 2) AS alone (n = 5), 3) O2 alone (n = 6), and 4) O2 + AS (n = 9). In the second series, we measured the wet-to-dry weight ratio (W/D) as an index of lung water and the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) as indexes of pulmonary endothelial damage. Cell accumulation in BAL fluid and lung tissue samples was also assessed in the second series.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Persistent Acute Inflammation at the Implant-Abutment Interface

Journal of Dental Research ◽

10.1177/154405910308200316 ◽

2003 ◽

Vol 82 (3) ◽

pp. 232-237 ◽

Cited By ~ 213

Author(s):

N. Broggini ◽

L.M. McManus ◽

J.S. Hermann ◽

R.U. Medina ◽

T.W. Oates ◽

...

Keyword(s):

Bone Loss ◽

Polymorphonuclear Leukocytes ◽

Acute Inflammation ◽

Inflammatory Cell ◽

Inflammatory Cells ◽

The Third ◽

Initial Surgery ◽

Cell Accumulation ◽

Implant Abutment ◽

Neutrophilic Polymorphonuclear Leukocytes

The inflammatory response adjacent to implants has not been well-investigated and may influence peri-implant tissue levels. The purpose of this study was to assess, histomorphometrically, (1) the timing of abutment connection and (2) the influence of a microgap. Three implant designs were placed in the mandibles of dogs. Two-piece implants were placed at the alveolar crest and abutments connected either at initial surgery (non-submerged) or three months later (submerged). The third implant was one-piece. Adjacent interstitial tissues were analyzed. Both two-piece implants resulted in a peak of inflammatory cells approximately 0.50 mm coronal to the microgap and consisted primarily of neutrophilic polymorphonuclear leukocytes. For one-piece implants, no such peak was observed. Also, significantly greater bone loss was observed for both two-piece implants compared with one-piece implants. In summary, the absence of an implant-abutment interface (microgap) at the bone crest was associated with reduced peri-implant inflammatory cell accumulation and minimal bone loss.

Download Full-text

Effect of doxycycline on sulfur mustard-induced respiratory lesions in guinea pigs

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00475.2004 ◽

2005 ◽

Vol 289 (1) ◽

pp. L67-L74 ◽

Cited By ~ 36

Author(s):

Christophe Guignabert ◽

Laurent Taysse ◽

Jean-Henri Calvet ◽

Emmanuelle Planus ◽

Séraphin Delamanche ◽

...

Keyword(s):

Guinea Pigs ◽

Inflammatory Cell ◽

Sulfur Mustard ◽

Chemical Warfare Agent ◽

Tissue Inhibitors Of Metalloproteinases ◽

Therapeutic Tool ◽

Gelatinase Activity ◽

In Situ Zymography ◽

Epithelial Lesions

Respiratory tract lesions induced by the chemical warfare agent sulfur mustard (SM) are characterized by epithelial damages associated with inflammatory cell infiltration. Here we evaluated the imbalance between gelatinase and tissue inhibitors of metalloproteinases (TIMPs), and we tested pretreatment with the protease inhibitor doxycycline. Guinea pigs were intoxicated intratracheally with SM and evaluated 24 h after exposure. Matrix metalloproteinase (MMP) gelatinase activity of bronchial lavage (BL) fluid from SM-exposed guinea pigs was high compared with controls, as shown by both zymography and biotinylated substrate degradation, whereas TIMP-1 and -2 levels by immunoblotting were similar. Extensive areas of lysis were evidenced by in situ zymography, indicating imbalance between gelatinases and inhibitors towards net proteolytic activity. Doxycycline pretreatment resulted in 1) decreased gelatinase activity (zymography, free gelatinase activity assay, and in situ zymography); 2) decreased inflammation (BL fluid cellularity and protein level); and 3) dramatic decrease in histological epithelial lesions. Our results suggest inadequate levels of TIMP to counteract increased gelatinase activity and further support a role for MMP gelatinases in SM-induced respiratory lesions. They also suggest that doxycycline may hold promise as a therapeutic tool.

Download Full-text

Elevated Plasma Level of Interferon-λ1 in Chronic Spontaneous Urticaria: Upregulated Expression in CD8+and Epithelial Cells and Induction of Inflammatory Cell Accumulation

Mediators of Inflammation ◽

10.1155/2016/5032051 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

S. F. Wang ◽

X. Q. Gao ◽

Y. N. Xu ◽

D. N. Li ◽

H. Y. Wang ◽

...

Keyword(s):

Mast Cells ◽

Inflammatory Cell ◽

Inflammatory Cells ◽

Chronic Spontaneous Urticaria ◽

Intercellular Adhesion Molecule ◽

Double Labeling ◽

Cell Accumulation ◽

Healthy Control ◽

Dose Dependent Increase ◽

Dose Dependent

Interferon- (IFN-)λ1 is regarded as a potent bio-active molecule in innate immunity. However, little is known about its role in chronic spontaneous urticaria (CSU). We therefore investigated expression of IFN-λ1 in CSU, its cellular location, and its influence on inflammatory cell accumulation by using flow cytometry analysis, skin tissue dispersion, immunohistochemical stain, and a mouse peritoneal inflammation model. The results showed that level of IFN-λ1 was 2.0-fold higher in plasma of the patients with CSU than the level in healthy control (HC) subjects. Among leukocytes examined, only CD8+T cells expressed more IFN-λ1 in CSU blood. Double labeling immunohistochemical staining revealed that IFN-λ1+inflammatory cells such as mast cells, eosinophils, B cells, neutrophils, and macrophages were mainly located in dermis, whereas epidermis tissue highly expressed IFN-λ1. IFN-λ1 induced a dose-dependent increase in number of eosinophils, lymphocytes, mast cells, macrophages, and neutrophils in the peritoneum of mice at 6 h following injection, which was inhibited by pretreatment of the animals with anti-intercellular adhesion molecule- (ICAM-) 1 and/or anti-L-selectin antibodies. In conclusion, IFN-λ1 is likely to play a role in the pathogenesis of CSU. Blocking IFN-λ1 production may help to reduce the accumulation of inflammatory cells in the involved CSU skin.

Download Full-text