Novel Anti-bacterial Activities of β-defensin 1 in Human Platelets: Suppression of Pathogen Growth and Signaling of Neutrophil Extracellular Trap Formation

PLoS Pathogens

Zechariah Franks¹  Peter Seizer²  Guy A. Zimmerman³  Robert A. Campbell³  Mark J. Cody⁴  Hansjörg Schwertz⁴  Neal D. Tolley⁴  Bjoern F. Kraemer⁴  Walter H. A. Kahr⁴  Stephan Lindemann⁴  Andrew S. Weyrich⁴  Christian C. Yost⁵ 

[1] Department of Surgery, University of Utah, Salt Lake City, Utah, United States of America;Division of Haematology/Oncology, Program in Cell Biology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Ontario, Canada;Medizinische Klinik III, Universitaetsklinikum Tuebingen, Tuebingen, Germany;Molecular Medicine Program, University of Utah, Salt Lake City, Utah, United States of America;The Petri-Hospital, Warburg, Germany

关键词: Platelets;    Staphylococcus aureus;    Neutrophils;    Defensins;    Platelet activation;    Bacterial growth;    Immunoprecipitation;    Megakaryocytes;   

DOI  :  10.1371/journal.ppat.1002355

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria.

【 授权许可】

CC BY