pr-39 and Bacterial-Infections

Host defense peptides (HDPs) are a large group of innate immune effectors that are also termed antimicrobial peptides. Because of the rapid progress that has been made in completing several animal genomes, many HDPs have been systemically defined using bioinformatic analysis and partially characterized using reverse genomic approaches. In pigs, about 30 HDPs have been identified and partially characterized relative to structure and function. Antimicrobial activity of porcine HDPs has been extensively evaluated against a broad spectrum of microorganisms in vitro and evaluated for their protective role in vivo. Increasing evidence indicates that HDPs are functionally differentiated during posttranslational and postsecretory processing, and that the structural units for antimicrobial and immunoregulatory functions are separate. These findings suggest promising new avenues for therapeutic drug design based on HDPs, including porcine HDPs. This review summarizes and discusses advances in porcine HDPs research during the last decade with an emphasis on the rapidly expanding profiles and biological functions.

Topics: Animals; Antimicrobial Cationic Peptides; Bacterial Infections; beta-Defensins; Cathelicidins; Chickens; Dogs; Host-Pathogen Interactions; Humans; Immunity, Innate; Immunologic Factors; Phylogeny; Species Specificity; Structure-Activity Relationship; Swine; Wound Healing

Skin is a substantial immune organ and represents the most important barrier against the potentially hostile environment. Its first line of defense are effector molecules of the innate immune system, which in contrast to the adaptive immune system reacts immediately against penetrating pathogenic microbes. Antimicrobial peptides represent the basis of the phylogenetically oldest part of the immune system. New studies show that reduced local cutaneous expression of antimicrobial peptide in burned skin is involved in the higher incidence of wound infections. The epithelium has an essential function in recognizing colonies of micro-organisms and in initial antimicrobial defenses.

Topics: Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacterial Infections; Humans; Immunity, Active; Immunity, Innate; Neovascularization, Physiologic; Neutrophils; Peptides; Skin; Wound Infection

Endotoxin (a lipopolysaccharide (LPS) component of the Gram negative bacterial cell wall) induces sepsis in laboratory animals and is the cause of septic shock in patients. Tissues often develop necrotic regions, particularly in kidney and liver, thought to be directly the result of endotoxin-induced release of nitric oxide (NO). These studies investigated the potential of PR-39, an antibacterial peptide, as an alternative treatment for sepsis. Our rationale for these experiments was based on the knowledge that PR-39 inhibits the superoxide-producing NADH/NADPH-oxidase system, and also inhibits NOS. In a mouse model of sepsis, we carried out EPR measurements of liver pO2 and NO simultaneously in vivo. Physiological parameters were also measured in these animals (blood pressure, heart rate). NO levels in blood were measured by EPR analysis of red blood cell nitrosyl-hemoglobin. We found PR-39 alleviated endotoxin-induced liver hypoxia 6 hrs after treatment. Tissue NO was higher in the PR-39 + LPS group compared to LPS alone. Circulating levels of NO were the same in these groups. Taken together, these results suggest PR-39 is effective in improving survival following a septic episode. The exact mechanism is unclear, but increased NO as a result of decreased superoxide production seems to play an important role in alleviating tissue hypoxia.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacterial Infections; Hypoxia; Male; Mice; Mice, Inbred BALB C; Sepsis; Spin Labels