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  • Author or Editor: Philip N. Bochsler x
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Abstract

Objective

To investigate the effects of anti-inflammatory drugs on lipopolysaccharide-induced procoagulant activity of bovine alveolar macrophages.

Design

Procoagulant activity was induced in bovine alveolar macrophages from 4 healthy Holstein calves aged 6 to 16 weeks by incubation with lipopolysaccharide. 3 anti-inflammatory drugs were used at 4 concentrations and 3 times to pretreat the alveolar macrophages. Results were analyzed to determine whether drug, concentration, or exposure period had a significant (P> 0.05) effect.

Procedure

Bovine alveolar macrophages, harvested by volume-controlled bronchoalveolar lavage, were pretreated for 30, 60, or 120 minutes with an anti-inflammatory compound (dexamethasone, flunixin meglumin, or phenylbutazone) at several concentrations (0, 1, 10, and 100 μM). Bovine alveolar macrophages were exposed to lipopolysaccharide (Escherichia coli O55:B5) in the presence and absence of fetal bovine serum for 4 hours. Procoagulant activity was measured, using a chromogenic assay.

Results

None of the drugs was associated with a modification of procoagulant activity expression.

Conclusion

Use of these 3 anti-inflammatory drugs is unlikely to modify the extent of the fibrinous reaction commonly observed in cases of acute bovine respiratory tract disease complex.

Clinical Relevance

The alveolar macrophage has a key role in fibrin production. Assuming in vivo events mimic the in vitro model, is appears unlikely that administration of anti-inflammatory drugs will reduce the procoagulant activity of the bovine alveolar macrophages and the directly associated pulmonary fibrosis. (Am J Vet Res 1996; 57:659–663)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To compare prevalence of organisms and histologic changes in eyes from dogs with blastomycosis that were either untreated or undergoing treatment with itraconazole.

Design—Retrospective study.

Animals—36 dogs with endophthalmitis associated with blastomycosis.

Procedure—Signalment, results of ophthalmic examination, and duration of treatment with itraconazole were extracted from medical records. Histologic sections from eyes were examined for prevalence and viability (ie, budding) of fungal organisms. A scoring system was devised to assess the degree of inflammation.

Results—Clinically, all eyes were blind and had signs of severe endophthalmitis. Histologically, the type and degree of inflammation and prevalence of Blastomyces dermatitidis were not significantly different between dogs treated with itraconazole and untreated dogs or among groups of dogs treated for different time periods (4 to 14, 15 to 28, or 29 to 72 days). Replication of the organisms in vascular tissues as well as avascular spaces in the eyes was similar in treated and untreated dogs. Lens rupture was seen in 12 of 29 (41%) eyes.

Conclusions and Clinical Relevance—Persistence of inflammation in eyes of dogs with naturally occurring blastomycosis is likely attributable to the continued presence of B dermatitidis, regardless of the duration of treatment with itraconazole. Lens capsule rupture, a common and previously unreported histologic finding, may contribute to cataract formation and continued inflammation. (J Am Vet Med Assoc 2004; 224:1317–1322)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective

To investigate receptor-mediated intracellular events in bovine alveolar macrophages (AM) stimulated by bacterial lipopolysaccharide (LPS), using tissue factor (TF) expression as the measurable functional endpoint.

Sample Population

Pulmonary AM harvested from 1- to 4-month-old male Holstein calves.

Procedure

Alveolar macrophages, acquired by use of volume-controlled bronchopulmonary lavage, were treated with CD14 monoclonal antibody (20 μg/ml), pertussis toxin (300 ng/ml), or 1 of 3 known protein kinase C (PKC) inhibitors (10 μM chelerythrin, 100 μM H-7, or 50 nM staurosporin), then were stimulated with LPS alone (0.01, 0.10, 1.0, 10.0 μg/ml) or LPS (0.25, 0.5, 1.0 ng/ml) in combination with concentrated bovine serum fraction 2 (500 ng/ml). Tissue factor expression was quantified by use of a colorimetric assay. Changes in intracellular Ca2+ concentration and pH were monitored, using Ca2+- and pH-sensitive fluorescent dyes, with changes in fluorescent intensity after incubation with LPS measured by spectrophotometry.

Results

Treatment of AM with a CD14 monoclonal antibody caused profound inhibition of TF expression (P < 0.0001) after stimulation by LPS combined with bovine serum fraction 2. Pertussis toxin had a significant (P < 0.0319) inhibitory effect on TF expression when cells were stimulated by LPS alone. Treatment with all 3 PKC inhibitors caused marked reduction in TF expression of cells stimulated with LPS alone or with phorbol myristate acetate. Stimulation of cells by LPS failed to mobilize intracellular Ca2+ stores or to alter cytosolic pH.

Conclusion

LPS combined with serum factors binds to CD14 on the surface of AM, and PKC is an important signaling kinase in the pathway utilized by LPS, resulting in enhanced TF expression; a pertussis toxin-sensitive G protein is involved in the signaling pathway utilized by LPS alone; and mobilization of Ca2+ does not have a role in the signal transduction pathway utilized by LPS nor does LPS affect cytosolic pH of AM. (Am J Vet Res 1998;59:445–451)

Free access
in American Journal of Veterinary Research