Lawrence J. Druhan

Leucine rich α-2 glycoprotein: A novel neutrophil granule protein and modulator of myelopoiesis

Leucine-rich α2 glycoprotein (LRG1), a serum protein produced by hepatocytes, has been implicated in angiogenesis and tumor promotion. Our laboratory previously reported the expression of LRG1 in murine myeloid cell lines undergoing neutrophilic granulocyte differentiation. However, the presence of LRG1 in primary human neutrophils and a role for LRG1 in regulation of hematopoiesis have not been previously described. Here we show that LRG1 is packaged into the granule compartment of human neutrophils and secreted upon neutrophil activation to modulate the microenvironment. Using immunofluorescence microscopy and direct biochemical measurements, we demonstrate that LRG1 is present in the peroxidase-negative granules of human neutrophils. Exocytosis assays indicate that LRG1 is differentially glycosylated in neutrophils, and co-released with the secondary granule protein lactoferrin. Like LRG1 purified from human serum, LRG1 secreted from activated neutrophils also binds cytochrome c. We also show that LRG1 antagonizes the inhibitory effects of TGFβ1 on colony growth of human CD34+ cells and myeloid progenitors. Collectively, these data invoke an additional role for neutrophils in innate immunity that has not previously been reported, and suggest a novel mechanism whereby neutrophils may modulate the microenvironment via extracellular release of LRG1.

Acute Heart Failure in a Patient with Acute Myeloid Leukemia following Daunorubicin Treatment: a Case Report

Heart failure following anthracycline treatment is usually chronic, irreversible, and related to life time dose. We present a patient with Acute Myeloid Leukemia (AML) who developed Heart failure soon after dose intensified treatment with daunorubicin, with a decrease in Ejection Fraction (EF) from 60% to as low as 10% six months after initial treatment. The patient was managed medically, his EF increased to greater than 50%. With this improvement in EF the patient was treated with reinduction chemotherapy and proceeded to hematopoietic stem cell transplantation. Following transplantation, the patient again developed heart failure, which contributed to his death. While anthracycline dose intensification can be effective in the treatment of AML, there is a risk of heart failure which requires further study.

Nitric Oxide, Sports Nutrition and Muscle Building

Nitric oxide (NO) is a gaseous signaling molecule that regulates many cellular functions, including the function of skeletal muscle. NO can be formed in skeletal muscle either by the activity of nitric oxide synthase enzymes or by the reduction of nitrite. The molecular mechanisms regulated by NO in skeletal muscle include mechanisms that are involved in or regulate muscle growth, including skeletal muscle blood flow, transcription of skeletal muscle proteins, activation of skeletal muscle satellite cells, and mitochondrial biogenesis. As such, nutritional supplementation with substances to increase skeletal muscle NO signaling has been hypothesized to increase both athletic performance and muscle growth. While several studies have demonstrated that enhancement of skeletal muscle NO signaling can increase exercise performance, there is a lack of data directly indicating that nutritional supplementation of skeletal muscle NO can affect muscle growth.