Distinctive Roles and Mechanisms of Human Neutrophil Peptides in Experimental Sepsis and Acute Respiratory Distress Syndrome
| Autor: | John Marshall, Florence Morriello, Yongbo Huang, Zhong Nanshan, Xiao-Yan Wen, Patricia C. Liaw, Julie Khang, Bing Han, Alice Luo, Haibo Zhang, Vito Fanelli, Xiangdong Guan, Mirna Ghazarian, Li Yimin, Arthur S. Slutsky, Jianfeng Wu, Dingyan Wang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Receptor complex medicine.medical_treatment Inflammation Lung injury Critical Care and Intensive Care Medicine Sepsis Mice 03 medical and health sciences medicine Animals Humans Cells Cultured Respiratory Distress Syndrome basal cell adhesion molecule Lung biology business.industry Friend virus Epithelial Cells medicine.disease biology.organism_classification infection alpha-defensins Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cytokine inflammation Alveolar Epithelial Cells Immunology Signal transduction medicine.symptom business |
| Zdroj: | Critical Care Medicine. 46:e921-e927 |
| ISSN: | 0090-3493 |
| Popis: | Objectives To examine the effects and mechanisms of human neutrophil peptides in systemic infection and noninfectious inflammatory lung injury. Design Prospective experimental study. Setting University hospital-based research laboratory. Subjects In vitro human cells and in vivo mouse models. Interventions Wild-type (Friend virus B-type) and conditional leukocyte human neutrophil peptides transgenic mice were subjected to either sepsis induced by cecal ligation and puncture or acute lung injury by intratracheal instillation of hydrochloric acid followed by mechanical ventilation. Using human neutrophil peptides as bait, the basal cell adhesion molecule (CD239) and the purinergic P2Y purinoceptor 6 receptor were identified as the putative human neutrophil peptides receptor complex in human lung epithelial cells. Measurements and main results In the cecal ligation and puncture sepsis model, Friend virus B-type mice exhibited higher systemic bacterial load, cytokine production, and lung injury than human neutrophil peptides transgenic mice. Conversely, an increased lung cytokine production was seen in Friend virus B-type mice, which was further enhanced in human neutrophil peptides transgenic mice in response to two-hit lung injury induced by hydrochloric acid and mechanical ventilation. The human neutrophil peptides-mediated inflammatory response was mediated through the basal cell adhesion molecule-P2Y purinoceptor 6 receptor signal pathway in human lung epithelial cells. Conclusions Human neutrophil peptides are critical in host defense against infectious sepsis by their cationic antimicrobial properties but may exacerbate tissue injury when neutrophil-mediated inflammatory responses are excessive in noninfectious lung injury. Targeting the basal cell adhesion molecule/P2Y purinoceptor 6 signaling pathway may serve as a novel approach to attenuate the neutrophil-mediated inflammatory responses and injury while maintaining the antimicrobial function of human neutrophil peptides in critical illness. |
| Databáze: | OpenAIRE |
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