Amniotic fluid eicosanoids in preterm and term births: effects of risk factors for spontaneous preterm labor.

Objective: To evaluate amniotic fluid arachidonic acid metabolites using enzymatic and nonenzymatic (lipid peroxidation) pathways in spontaneous preterm birth and term births, and to estimate whether prostanoid concentrations correlate with risk factors (race, cigarette smoking, and microbial invasion of amniotic cavity) associated with preterm birth.

Methods: In a case-control study, amniotic fluid was collected at the time of labor or during cesarean delivery. Amniotic fluid samples were subjected to gas chromatography, negative ion chemical ionization, and mass spectrometry for prostaglandin (PG) E2, PGF2α, and PGD2 and for 6-keto-PGF1α (thromboxane 2 and F2-isoprostane).

PTEN limits alveolar macrophage function against Pseudomonas aeruginosa after bone marrow transplantation.

Hematopoietic stem cell transplant patients are susceptible to infection despite cellular reconstitution. In a murine model of syngeneic bone marrow transplantation (BMT), we previously reported that BMT mice have impaired host defense against Pseudomonas aeruginosa pneumonia due to overproduction of (PG)E(2) in lung. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an effector in the PGE(2) signaling pathway that negatively regulates alveolar macrophage (AM) phagocytosis and bacterial killing.

Impaired pulmonary immunity post-bone marrow transplant.

Infectious complications are a serious cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT), and the lung is a particular target organ post-transplant. Our laboratory has used a murine bone marrow transplant model to study alterations in immunity that occur as a result of transplantation. Our studies focus on immune responses that occur following immune cell reconstitution in the absence of immunosuppressive drug therapy or graft-versus-host disease.

A role for IL-1 receptor-associated kinase-M in prostaglandin E2-induced immunosuppression post-bone marrow transplantation.

Following immune reconstitution, hematopoietic stem cell transplant patients often display reduced immune function and are especially susceptible to lung infections. In a mouse model of syngeneic bone marrow transplantation (BMT), we previously reported that PGE(2) is overproduced in lungs of BMT mice, significantly impairing host defense against Pseudomonas aeruginosa. This impairment in host defense post-BMT is also marked by diminished alveolar macrophage (AM) phagocytosis, bacterial killing, and production of TNF-alpha and cysteinyl leukotrienes.

IRAK-M regulation and function in host defense and immune homeostasis.

Antigen presenting cells (APCs) of the innate immune system sense a wide range of pathogens via pattern recognition receptors (PRRs). Engagement of certain PRRs can induce production of pro-inflammatory mediators that facilitate effective clearance of pathogen. Toll-like receptors (TLRs) are a well described group of PRRs that belong to the TLR/Interleukin-1 receptor (IL-1R) superfamily.

Comprehensive analysis of single-repeat R3 MYB proteins in epidermal cell patterning and their transcriptional regulation in Arabidopsis.

Background: Single-repeat R3 MYB transcription factors are critical components of the lateral inhibition machinery that mediates epidermal cell patterning in plants. Sequence analysis of the Arabidopsis genome using the BLAST program reveals that there are a total of six genes, including TRIPTYCHON (TRY), CAPRICE (CPC), TRICHOMELESS1 (TCL1), and ENHANCER of TRY and CPC 1, 2, and 3 (ETC1, ETC2 and ETC3) encoding single-repeat R3 MYB transcription factors that are approximately 50% identical to one another at the amino acid level. Previous studies indicate that these single-repeat R3 MYBs regulate epidermal cell patterning.

Comparison of conditioning regimens for alveolar macrophage reconstitution and innate immune function post bone marrow transplant.

The authors compared efficiency of alveolar macrophage (AM) reconstitution from donor bone marrow post transplant following 4 chemotherapy conditioning regimens and 2 total body irradiation (TBI) regimens. TBI regimens are more effective in inducing AM reconstitution from donor marrow. However, mice conditioned with 13 Gy split-dose TBI or a dual-chemotherapy regimen (25 mg/kg busulfan x 4 days plus cyclophosphamide 100 mg/kg x 2 days) both demonstrate significant AM repopulation from donor marrow.

Paradoxical role of alveolar macrophage-derived granulocyte-macrophage colony-stimulating factor in pulmonary host defense post-bone marrow transplantation.

Impaired host defense post-bone marrow transplant (BMT) is related to overproduction of prostaglandin E(2) (PGE(2)) by alveolar macrophages (AMs). We show AMs post-BMT overproduce granulocyte-macrophage colony-stimulating factor (GM-CSF), whereas GM-CSF in lung homogenates is impaired both at baseline and in response to infection post-BMT. Homeostatic regulation of GM-CSF may occur by hematopoietic/structural cell cross talk.