Biomedical subjects

Amy Martin

Publications and source records attributed to Amy Martin.

3 recordsLinked to original sources

PubMed2005

Molecular basis for the potency of IL-10-deficient dendritic cells as a highly efficient APC system for activating Th1 response.

Identification and targeting of novel immunobiological factors that regulate the induction of Th1 cells are crucial for designing effective vaccines against certain intracellular pathogens, including Chlamydia. IL-10-deficient dendritic cells (DC) are potent APCs and effective cellular vaccines that activate a high frequency of specific Th1 cells. To elucidate the molecular basis for the potency of the IL-10-deficient APC system, we tested the hypothesis that Chlamydia Ag-primed IL-10 knockout (IL-10KO) DC are quantitatively and qualitatively distinct in their metabolic characteristics relating to T cell activation. Using a combination of RT-PCR, two-dimensional gel electrophoresis, and MALDI-TOF-based proteomics analyses, the transcriptional and translational activities of Chlamydia-pulsed DC from wild-type and IL-10KO mice were assessed. IL-10 deficiency caused early maturation and activation of pulsed DC (i.e., high CD11c, CD40, CD80, CD83, CD86, IL-1, IL-12, and the T cell-attracting chemokine CCL27/CTACK) and consequently an enhanced ability to process and present Ags for a rapid and robust T cell activation. Supporting comparative proteomics revealed further that IL-10 deficient DC possess specific immunobiological properties, e.g., the T cell-attracting chemokine CCL27/CTACK, calcium-dependent protein kinase, and the IL-1/IL-12 inducer, NKR-P1A (CD161), which differentiated them immunologically from wild-type DC that express molecules relating to anti-inflammatory, differentiative, and metabolic processes, e.g., the anti-IL-12 molecule peroxisome proliferator-activated receptor-alpha and thymidine kinase. Collectively, these results provide a molecular basis for the high Th1-activating capacity of IL-10KO APC and may provide unique immunomodulation targets when designing vaccines against pathogens controlled by T cell immunity.

Animals↗

PubMed2004

Stress causes a further decrease in immunity to herpes simplex virus-1 in immunocompromised hosts.

Physical or psychological stress can modulate immune responses in normal subjects. The effects of stress on immunity in immunocompromised hosts, however, have not been extensively investigated. Here we assess relationships among footshock stress (FS), infection with herpes simplex virus-1 (HSV-1), and immunosuppression by cyclophosphamide (CY) during the active immune response to virus in BALB/c mice. Without FS, CY significantly decreased survival and body weight gain, splenic leukocyte numbers, in vivo serum cytokine level and in vitro splenocyte cytokine production during HSV-1 infection. FS alone also significantly inhibited cell mediated anti-viral responses to HSV-1. However, FS in combination with certain CY doses led to a further significant decrease in host responses compared to either CY or FS treatment alone, including decreased survival rate, increased weight loss, lowered leukocyte numbers, reduced cytokine production in vivo and in vitro, and decreased numbers of cytokine-producing cells (IL-12 and IFNgamma). In contrast, CY, but not FS, significantly reduced in vivo anti-HSV-1 antibody secretion. These data support the hypothesis that stress can further reduce host immune responses in immunocompromised individuals. Thus, stress levels of patients should be taken into consideration prior to clinical treatment with immunosuppressants.

Animals↗

PubMed2002

Pulmonary siderophages and unexpected infant death.

It has been proposed that the presence of siderophages in the lungs of infants who die unexpectedly should be considered a marker of a previous hypoxic event, which may preclude a diagnosis of sudden infant death syndrome. The authors retrospectively reviewed all infant deaths (<1 year old) going to autopsy at the Denver Office of the Medical Examiner from January 1999 to January 2001. Lung sections were stained with Prussian blue, and siderophages were counted in 20 high-power fields per lobe sampled. Cell counts were performed by two independent pathologists who were blinded to history and cause of death, with good reproducibility. Iron stain results were then categorized by average number of siderophages per 20 high-power field (category 1 = <5, category 2 = 5-100, category 3A = 100-500, category 3B = >100 in a single lobe, category 4 = >500). The results were subsequently correlated to case history, autopsy findings, and cause/manner of death. Forty-three cases were reviewed. The causes of death included sudden infant death syndrome (16), asphyxia (5), undetermined (6), and other (16). Those deaths were categorized by the above criteria as follows: category 1. (32), category 2. (6), category 3. (4), and category 4. (1). All sudden infant death syndrome deaths were in category 1. Categories 1 and 2 also included deaths in which hypoxia might have been present before death because of such factors as pneumonia and congenital heart disease. Categories 3 and 4 included a known homicidal asphyxia in which repeated episodes of intentional smothering were documented, 2 probable asphyxias, 1 nonaccidental trauma, and 1 undetermined. All 5 cases had questionable circumstances surrounding the death of the infant. Pulmonary siderophages were described in only 1 of the 43 autopsy reports. It was concluded that pulmonary siderophages can be markedly increased in cases of repeated asphyxia. Siderophages may also be increased in cases where hypoxia may have been present for another reason, but not to the same degree. Siderophages are not increased in sudden infant death syndrome. Because iron-laden macrophages often are not recognized on routine examination with hematoxylin and eosin staining, iron stains may be helpful in the evaluation of infant deaths. If siderophages are present in increased amounts without an obvious explanation, further investigation is warranted.

Biomarkers↗