Pentraxin 3 in the lung and neutrophils
Date
2013-09-23
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Masters
Abstract
Respiratory diseases are a major cause of human morbidity and mortality and are a leading cause of economic loss to livestock producers. The respiratory tract is constantly in contact with dust, bacteria, fungi, viruses and other pathogenic agents that are found in the air. Normally, the body has the ability to clear these foreign particles. However, physiological and environmental stresses can impair airway defense mechanisms resulting in establishment of pulmonary infections. The microbes and their products engage various receptors in the lung to activate epithelium, endothelium, macrophages, neutrophils and other cells. The activation of inflammatory cascade in the lung results in recruitment of neutrophils, damage to air-blood barrier and development of edema. Although there have been significant advances in our understanding of mechanisms of lung inflammation, there have been a lack of any significant advances in the development of new therapeutics to manage lung disease, which may suggest that our understanding of the inflammatory mechanisms is still incomplete.
Pentraxin 3 (PTX3) is an innate immune protein which has been implicated in a diverse range of inflammatory processes, such as recruitment of cells and production of cytokines. PTX3 is an acute phase protein, with low or undetectable levels in the circulation of healthy humans and animals, and rapid, dramatic increase in inflammatory diseases. The expression and function of this protein has not been characterized in the lungs of domestic animal species. Because of potential implications of PTX3 in lung inflammation, I studied the expression of PTX3 in normal and inflamed lungs of calves, pigs, horses, foals and humans. Lungs from all of these species showed expression of PTX3 in airway epithelium, alveolar septa, vascular endothelium and inflammatory cells. Western blot performed on homogenates from normal and inflamed lungs from calves and pigs show an increased expression of PTX3 in inflamed lungs (P<0.05).
Because protein function is influenced by its location in the cell, I clarified the subcellular expression of PTX3 with immuno-electron microscopy on normal and inflamed calf and horse lungs. PTX3 was localized on pulmonary intravascular macrophages, monocytes, neutrophils and, unexpectedly, platelets. PTX3 was also present in the nuclei of neutrophils, monocytes and pulmonary intravascular macrophages.
Neutrophils are critical regulators of acute lung inflammation. Having observed PTX3 in neutrophils, I investigated the effect of E. coli lipopolysaccharide-induced activation on PTX3 in neutrophils in vitro. Neutrophils challenged with E. coli LPS were examined at 30, 60, 90 and 120 minutes after the treatment. Normal peripheral blood neutrophils showed PTX3 expression. Neutrophils activated with LPS appeared ruffled and showed loss of PTX3 expression at 30 minutes followed by recovery of the expression. Western blots performed on normal and activated neutrophil homogenates did not show any differences (P=0.05).
Collectively, the data show PTX3 in normal and inflamed lungs across multiple species. PTX3 was also detected in normal and activated neutrophils. While the function of intriguing localization of PTX3 in the nuclei as well as in platelets is not known, the similarity of expression across the species suggest a role for PTX3 in lung inflammation.
Description
Keywords
lung, respiratory disease, innate immune system, pattern recognition receptor, pentraxin 3, bovine, equine, human, porcine, inflammation
Citation
Degree
Master of Science (M.Sc.)
Department
Veterinary Biomedical Sciences
Program
Veterinary Biomedical Sciences