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Platelet-activating factor induces intestinal necrosis, but not septic shock, in germ-free and specific-pathogen-free
E J Schiffrin1, M Trop, S Schroeder
1Massachusetts General Hospital, Boston.
Abstract:
Platelet-activating factor (PAF) was injected into conventional mice, endotoxin-resistant mice (C3H/HEJ), conventional rats, germ-free rats and specific-pathogen-free (SPF) mice. The PAF resulted in significant necrosis and damage to the small intestines of all the animals tested. In general, the frequency and severity of the lesions were similar in all groups. All the conventional rats and mice, as well as the endotoxin-resistant HEJ mice, were dead 18 h after the injection of the PAF, while all the germ-free rats and the SPF mice survived. These data demonstrate that development of massive intestinal lesions, in the absence of aerobic bacteria, is not sufficient to cause the death of the host from septic shock and endotoxaemia.
Insights
Platelet-activating factor (PAF) caused severe intestinal damage in all tested animals. However, only animals with aerobic bacteria died, suggesting gut bacteria are crucial for PAF-induced septic shock.
Area of Science:
- Gastroenterology
- Immunology
- Microbiology
Background:
- Platelet-activating factor (PAF) is a potent lipid mediator involved in inflammation and immune responses.
- Intestinal injury can lead to systemic complications like septic shock and endotoxemia.
- The role of gut microbiota in the host's response to inflammatory mediators and subsequent mortality is not fully understood.
Purpose of the Study:
- To investigate the role of aerobic bacteria in the mortality of animals subjected to Platelet-activating factor (PAF)-induced intestinal injury.
- To determine if severe intestinal lesions alone are sufficient to cause death from septic shock and endotoxemia.
Main Methods:
- Platelet-activating factor (PAF) was administered to various animal models, including conventional mice, endotoxin-resistant mice (C3H/HEJ), conventional rats, germ-free rats, and specific-pathogen-free (SPF) mice.
- Animals were monitored for survival and the development and severity of intestinal lesions, specifically necrosis, at 18 hours post-injection.
- Comparative analysis of mortality rates and lesion severity across different animal groups based on their microbial status.
Main Results:
- PAF injection induced significant necrosis and damage to the small intestines in all tested animal groups.
- Mortality rates varied significantly: conventional and endotoxin-resistant mice/rats died within 18 hours, while germ-free and SPF rats/mice survived.
- The frequency and severity of intestinal lesions were comparable across all groups, irrespective of survival outcomes.
Conclusions:
- Massive intestinal lesions induced by PAF are not sufficient to cause host death in the absence of aerobic bacteria.
- The presence of aerobic gut bacteria appears to be a critical factor in the development of fatal septic shock and endotoxemia following PAF-induced intestinal injury.
- These findings highlight the essential role of the gut microbiome in modulating the host's response to inflammatory mediators and preventing systemic mortality.