Analysis of the mechanisms through which pathogenic mycobacteria interfere with macrophage activation and phagosome maturation have shown that engagement of specific membrane receptors with bacterial ligands is the initiating event. Mannosylated lipoarabinomannan (Man-LAM) has been identified as one of the ligands that modulates macrophage function. We evaluated the effects of Man-LAM derived from Mycobacterium avium subsp.
View Article and Find Full Text PDFMany therapeutic drugs have been associated with hematologic adverse drug events (ADEs) in animals. Some drugs, notably chemotherapeutic agents and oxidant compounds, cause dose-dependent bone marrow suppression, while others induce idiosyncratic ADEs. Major mechanisms associated with ADEs include immune- or oxidant-mediated destruction of blood cells and toxic bone marrow injury.
View Article and Find Full Text PDFObjective: To evaluate the role of the nuclear factor-kappaB (NF-kappaB) in the response of bovine monocytes to exposure to Mycobacterium avium subsp paratuberculosis (MAP).
Sample Population: Monocytes from healthy adult Holstein cows that were known to be negative for MAP infection.
Procedures: Monocytes were incubated with MAP organisms with or without a specific inhibitor of the NF-kappaB pathway (pyrrolidine dithiocarbamate), and activation of the NF-kappaB pathway was detected by use of an electrophorectic mobility shift assay.
Mycobacterium avium subsp. paratuberculosis (MAP), the agent of paratuberculosis, is a slow growing mycobacteria that survives within ruminant mononuclear phagocytes by preventing cell activation and phagosome maturation. We investigated interactions between MAP and monocyte membrane receptors that result in activation of the mitogen-activated protein kinase (MAPK) p38 pathway and suppression of monocyte antimicrobial activity.
View Article and Find Full Text PDFA 3-year-old Irish Wolfhound was evaluated because of acute onset of lethargy and fever. Severe neutropenia (0/microL; reference interval 2500-11,200/microL) was associated with granulocyte aplasia in the bone marrow (myeloid:erythroid ratio, 0.009:1).
View Article and Find Full Text PDFWe compared the kinetics of activation and antimicrobial activities of MAPK-p38 and MAPK-ERK in bovine monocytes infected with Mycobacterium avium subsp. paratuberculosis (MAP) and Mycobacterium avium subsp. avium (Maa).
View Article and Find Full Text PDFPathogenic mycobacterial organisms have the capacity to inhibit macrophage activation and phagosome maturation. Although the mechanism is complex, several studies have incriminated signaling through TLR2 receptors with subsequent activation of the MAPK pathway p38 (MAPKp38) and overproduction of IL-10 in the survival of pathogenic mycobacterial organisms. In the present study, we compared the response of bovine monocytes with infection by Mycobacterium avium subspecies paratuberculosis (MAP), the cause of paratuberculosis in ruminants, with the closely related organism M.
View Article and Find Full Text PDFObjective: To determine cell membrane receptors involved in phagocytosis of Mycobacterium avium subsp paratuberculosis (MAP) organisms.
Sample Population: Monocytes were obtained from healthy adult Holstein dairy cows that were test negative for MAP infection on the basis of bacteriologic culture of feces and serologic test results.
Procedures: Monocytes or bovine macrophage cell line (BoMac) cells were incubated with MAP organisms for 30, 60, or 120 minutes with or without inhibitors of integrins, CD14, or mannose receptors.
J Vet Intern Med
July 2007
Background: Immune-mediated neutropenia (IMN) is one of several causes of persistent neutropenia in dogs. A test to detect IMN in dogs is not available.
Hypothesis: A flow cytometric immunofluorescence assay will provide a sensitive method for detection of antineutrophil antibodies in dogs.
Objective: To evaluate the role of the mitogen-activated protein kinase extracellular signal-regulated kinase (MAPK(ERK)) pathway in the interaction between Mycobacterium avium subsp paratuberculosis (MAP) organisms and bovine monocytes.
Sample Population: Monocytes obtained from healthy adult Holstein dairy cows that were not infected with MAP organisms.
Procedures: Monocytes and MAP organisms were incubated together with or without a specific inhibitor of the MAPK(ERK) pathway (PD98059), and the capacity of monocytes to express tumor necrosis factor alpha (TNF)-alpha and interleukin (IL)-10 and -12, produce nitric oxide, acidify phagosomes, kill MAP organisms, and undergo apoptosis was evaluated.
Objective: To develop a clinically applicable assay for detection of serum anti-neutrophil antibodies in dogs.
Sample Population: Serum samples of 20 healthy dogs and 20 sick dogs.
Procedures: An indirect immunofluorescence assay was developed in which canine serum was incubated with paraformaldehyde-fixed neutrophils and subsequently incubated with fluorescein-conjugated rabbit anti-dog IgG.
Objective: To determine the frequency, potential causes, and clinical and clinicopathologic features of hemophagocytic syndrome in dogs.
Design: Retrospective study.
Animals: 24 client-owned dogs.
Vet Clin Pathol
December 2006
Background: Aplastic pancytopenia is defined by the presence of pancytopenia in blood and a hypocellular bone marrow with the hematopoietic space replaced by adipose tissue. Several causes of acquired aplastic pancytopenia are known; however, in some cases, an underlying cause is never determined.
Objective: The objective of this retrospective study was to identify the incidence, potential causes, and outcome of aplastic pancytopenia in dogs.
Objective: To evaluate activation of Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway in bovine monocytes after incubation with Mycobacterium avium subsp paratuberculosis (Mptb) organisms.
Sample Population: Bovine monocytes obtained from 4 healthy adult Holstein dairy cows.
Procedures: Bovine monocytes were incubated with Mptb organisms with or without a specific inhibitor of the JNK/SAPK pathway (SP600125) for 2, 6, 24, or 72 hours.
Background: An 8-year retrospective study was conducted to evaluate the prevalence and the classification of canine bone marrow disorders in a clinical pathology service at a university referral hospital.
Animals: Dogs evaluated for bone marrow disorders at a veterinary teaching hospital.
Hypothesis: A better understanding of the spectrum and the prevalence of canine bone marrow disorders can be achieved with a multiyear retrospective study.
Thromboembolism is a major cause of morbidity and mortality in dogs with immune-mediated hemolytic anemia (IMHA). To the authors' knowledge, the role of platelets in thromboembolic events associated with IMHA has not been extensively investigated. In the study reported here, we evaluated cell membrane expression of P-selectin with flow cytometry to determine whether platelets circulate in an activated state in association with primary IMHA.
View Article and Find Full Text PDFWe investigated the role of cell signaling through the mitogen-activated protein kinase-p38 (MAPK p38) pathway on the antimicrobial functions and cytokine expression by bovine monocytes after ingestion of Mycobacterium avium subsp. paratuberculosis. We evaluated the dynamic secretion of interleukin (IL)-10, IL-12 and tumor necrosis factor-alpha (TNF-alpha) as well as phagosome acidification and organism killing at several time points after in vitro infection of bovine monocytes with M.
View Article and Find Full Text PDFObjective: To further classify dysmyelopoiesis as diagnosed by use of a general classification scheme and to determine clinical features and laboratory test results that could be used to differentiate between the various forms of dysmyelopoiesis in cats.
Design: Retrospective case series. Sample Population-Bone marrow slides from 34 cats.
A retrospective study of 128 feline bone marrow reports identified 13 cases of aplastic anemia. Clinical diagnoses included chronic renal failure (n=5), feline leukemia virus infection (n=2), hyperthyroidism treated with methimazole (n=1) and idiopathic aplastic anemia (n=5). In some cats, starvation may play a role in the development of marrow aplasia.
View Article and Find Full Text PDFJ Vet Intern Med
February 2006
Differentiation of benign and malignant causes of lymphocytosis in blood or bone marrow can be problematic. In the present study, reports of examinations of bone marrow from cats, submitted over an 8-year period, were reviewed to identify cats with increased numbers of small lymphocytes. Of 203 reports reviewed, 12 (5.
View Article and Find Full Text PDFObjective: To determine functional characteristics of monocytes obtained from cows with subclinical infection with Mycobacterium avium subsp paratuberculosis (MAP) that may have predisposed those cows to becoming infected with MAP SAMPLE POPULATION: Monocytes obtained from 5 uninfected cows and 5 cows subclinically infected with MAP in a herd with a high prevalence of paratuberculosis (ie, Johne's disease).
Procedures: Monocytes from uninfected and subclinically infected cows were incubated with MAP for 2, 6, 24, 72, or 96 hours. Variables measured included expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-10, IL-12, transforming growth factor-beta, and suppressor of cytokine signaling-3 (SOCS-3); apoptosis of monocytes; acidification of phagosomes; and killing of MAP.
Objective: To identify the incidence, potential causes, and clinical and clinicopathologic features of bone marrow necrosis in dogs.
Design: Retrospective study.
Animals: 34 client-owned dogs.
Sideroblastic anemia is an anemic condition characterized by chronic hypochromic anemia and the presence of large iron deposits in erythroid cells. Seven dogs with sideroblastic anemia were evaluated retrospectively. Historical, clinical, and clinicopathologic findings were reviewed to determine whether the condition was idiopathic or associated with disease conditions or drug or toxin exposure.
View Article and Find Full Text PDFObjectives: To evaluate the role of interleukin (IL)-10 in the inability of monocyte-derived bovine macrophages to kill Mycobacterium avium subsp paratuberculosis organisms in vitro.
Sample Population: Monocytes were obtained from healthy adult Holstein dairy cows that had negative results when tested for infection with M avium subsp paratuberculosis.
Procedure: Monocyte-derived macrophages were incubated with M avium subsp paratuberculosis for 2, 6, 24, 72, or 96 hours with or without addition of saturating concentrations of a goat anti-human IL-10 that has been documented to neutralize bovine IL-10 activity.
Dysmyelopoiesis is defined as a hematologic disorder characterized by the presence of cytopenias in the blood and dysplastic cells in one or more hematologic cell lines in the blood or bone marrow. The causes of dysmyelopoiesis include acquired mutations in hematopoietic stem cells (i.e.
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