Adult Respiratory Distress Syndrome (ARDS) is a form of acute lung injury characterized by refractory hypoxemia and high permeability pulmonary edema. Bacterial pneumonia is a complication which can result in sepsis and increased mortality rates in ARDS patients. A decrease in alveolar macrophage (AM) function has been demonstrated in several animal models of ARDS; a correlation between this decrease and an increased susceptibility of ARDS patients to nosocomial pneumonia has been proposed. The goal of this research is to define the pathophysiology of decreased AM function in endotoxin-induced lung injury and to determine whether modulating AM function with alveolar lining material and cytokines can overcome these decreased pulmonary host defenses. We will address this problem with the following Specific Aims: 1. Compare the relative importance of changes in the alveolar milieu vs. damage to the AM in decreasing AM function in endotoxin- induced lung injury. 2. Determine the importance that alterations in the alveolar lining material play in the impaired AM function seen in endotoxin- induced lung injury. 3. Evaluate the effects of exogenous cytokines on AM function in normal animals and in those with endotoxin-induced lung injury.
The specific aims of this proposal provide an intellectually challenging opportunity for me to investigate the pathophysiology of an important medical problem. Under the direction of prominent researchers in the local medical community, the proposed research also allows me to evaluate the potential of new therapeutic and/or prophylactic agents to improve decreased pulmonary host defenses. In addition to the proposed research, the comprehensive training program for the Doctor of Science degree at the Harvard School of Public Health will include coursework, laboratory training, and attendance at seminars and lectures. It is my goal to use this intensive research training to become an independent, creative researcher.
| Frevert, C W; Warner, A E; Weller, E et al. (1998) The effect of endotoxin on in vivo rat alveolar macrophage phagocytosis. Exp Lung Res 24:745-58 |
| Frevert, C W; Farone, A; Danaee, H et al. (1995) Functional characterization of rat chemokine macrophage inflammatory protein-2. Inflammation 19:133-42 |
| Frevert, C W; Warner, A E; Kobzik, L (1994) Defective pulmonary recruitment of neutrophils in a rat model of endotoxemia. Am J Respir Cell Mol Biol 11:716-23 |
