Activities of nonlysosomal proteolytic systems in skeletal and cardiac muscle during burn-induced hypermetabolism.

The aim of this study was to assess the activity of nonlysosomal proteolytic systems in skeletal and cardiac muscle during burn-induced hypermetabolism (BHM) in rats. Rats underwent 30% TBSA scald burn or sham injury and were observed for up to 42 days. Body weights and resting energy expenditures were determined weekly.

Dendritic cell depletion in burn patients is regulated by MafB expression.

Studies have shown that monocytes are hyporesponsive and that dendritic cells (DCs) are depleted in burn patients. We have recently shown in a mouse model that burn injury alters the transcriptional regulation in bone marrow progenitors and inhibits myeloid-derived DC (mDC) production. In the present study, using human burn patient peripheral blood mononuclear cells, we have shown an overexpression of MafB with a corresponding reduction in peripheral blood mononuclear cell-derived mDCs.

Nonviral human beta defensin-3 expression in a bioengineered human skin tissue: a therapeutic alternative for infected wounds.

The innate immune system differentially regulates the expression of host defense peptides to combat infection during wound healing. We enhanced the expression of a host defense peptide, human beta defensin-3 (hBD-3), in keratinocytes to generate a three-dimensional biologic dressing to improve healing of infected wounds. The NIKS human keratinocyte cell line was stably transfected ex vivo with a construct containing an epidermis-specific promoter driving hBD-3 (NIKS(hBD) (-3) ) using nonviral methods.

Burn injury dampens erythroid cell production through reprioritizing bone marrow hematopoietic response.

Background: Anemia in burn patients is due to surgical blood loss and anemia of critical illness. Because the commitment paradigm of common bone marrow progenitors dictates the production of erythroid, myeloid, and lymphoid cells, we hypothesized that skewed bone marrow lineage commitment decreases red cell production and causes anemia after a burn injury.

Methods: After anesthesia, B(6)D(2)F(1) mice received a 15% total body surface area dorsal scald burn.

Inhibition of multidrug-resistant Acinetobacter baumannii by nonviral expression of hCAP-18 in a bioengineered human skin tissue.

When skin is compromised, a cascade of signals initiates the rapid repair of the epidermis to prevent fluid loss and provide defense against invading microbes. During this response, keratinocytes produce host defense peptides (HDPs) that have antimicrobial activity against a diverse set of pathogens. Using nonviral vectors we have genetically modified the novel, nontumorigenic, pathogen-free human keratinocyte progenitor cell line (NIKS) to express the human cathelicidin HDP in a tissue-specific manner.

Propranolol restores the tumor necrosis factor-alpha response of circulating inflammatory monocytes and granulocytes after burn injury and sepsis.

Beta-adrenergic blockade ameliorates the hypermetabolism and catabolism in severe burn injury. Despite the salutary effects of beta-adrenergic blockade, the immunologic responses that accompany beta-blockade are not known. We have shown that burn sepsis is associated with increased sympathetic activation leading to altered monocytopoiesis and cytokine release in macrophages (MØ).

Severity of burn injury and sepsis determines the cytokine responses of bone marrow progenitor-derived macrophages.

Background: Although thermal injury and sepsis result in enhanced monocytopoiesis, the functional characteristics of macrophages that develop in the microenvironment of burn and sepsis are unknown. Here we compare cytokine responses of bone marrow progenitor-derived macrophages (BMO) and peritoneal macrophages (PMO) after graded levels of thermal injury and sepsis.

Methods: Mice were randomly divided into sham (S), burn (B), and burn sepsis (BS) groups.

A novel antibacterial gene transfer treatment for multidrug-resistant Acinetobacter baumannii-induced burn sepsis.

Sepsis caused by multidrug-resistant bacterial infections in critically injured patients has become a major clinical problem. Recently, Acinetobacter baumannii (AB) wound infections, especially in our critically injured soldiers fighting in Iraq and Afghanistan, is posing a major clinical problem and an economic burden. ConjuGon, Inc.

Burn injury and pulmonary sepsis: development of a clinically relevant model.

Background: Despite improvements in the early resuscitation of the critically injured, mortality from multiple organ failure has remained stable, with the lung often the first organ to fail. Early intubation and mechanical ventilation predispose patients to the development of pneumonia and respiratory failure. Our objective was to establish a murine model of combined injury, consisting of burn/trauma and pulmonary sepsis with reproducible end-organ responses and mortality.

Accelerated wound closure in neutrophil-depleted mice.

The infiltration of neutrophils into injured tissue is known to protect wounds from invading pathogens. However, more recent studies suggest that neutrophils might inhibit the wound repair process. To investigate the role of neutrophils in wounds, mice were neutrophil-depleted by injection with rabbit anti-mouse neutrophil serum.

Granulocyte colony-stimulating factor: release is not impaired after burn wound infection.

Background: The production of granulocyte colony-stimulating factor (G-CSF), the lineage specific essential regulator of neutrophil progenitor cell proliferation and differentiation, has been thought to be impaired in the setting of burn infection. The ability to directly measure murine G-CSF allows the further delineation of the G-CSF response in a clinically relevant model of thermal injury and infection.

Methods: We used a commercially available solid phase enzyme-linked immunoabsorbent assay to quantify G-CSF production after burn wound infection in mice.