Role of Mac-1 integrin in generation of extracellular vesicles with antibacterial capacity from neutrophilic granulocytes

• Published in: Journal of extracellular vesicles Vol. 9; no. 1; pp. 1698889 - n/a
• Main Authors: Lőrincz, Ákos M., Bartos, Balázs, Szombath, Dávid, Szeifert, Viktória, Timár, Csaba I., Turiák, Lilla, Drahos, László, Kittel, Ágnes, Veres, Dániel S., Kolonics, Ferenc, Mócsai, Attila, Ligeti, Erzsébet
• Format: Journal Article
• Language: English
• Published: Sweden Taylor & Francis 01.01.2020; John Wiley & Sons, Inc; Wiley
• Subjects: Bacteria; bacterial growth; Cell interactions; Complement activation; complement receptor; Complement receptor 3; EV biogenesis; Extracellular vesicles; Fc receptor; Fc receptors; Flow cytometry; Genetically engineered microorganisms; Granulocytes; inflammation; Leukocytes (granulocytic); Leukocytes (neutrophilic); Mac-1 integrin; Mac‐1 integrin; Microscopy; Neutrophils; Opsonin receptors; opsonins; Opsonization; Pattern recognition receptors; Proteins; Proteomics; Signal transduction; Transgenic animals; tyrosine kinase inhibitor; Hungary; United States > US; Germany; EV biogenesis; Fc receptor; extracellular vesicles; opsonins; complement receptor; inflammation; Neutrophils; Mac-1 integrin; tyrosine kinase inhibitor; bacterial growth
• ISSN: 2001-3078; 2001-3078
• DOI: 10.1080/20013078.2019.1698889

Production of extracellular vesicles (EVs) involved in intercellular communication is a common capacity of most cell types. Upon encountering opsonized microorganisms, neutrophilic granulocytes release EVs that compromise bacterial growth. We carried out a systematic investigation of the involvement of potential opsonin receptors in EV-generation from human and murine neutrophils. Applying flow cytometric, proteomic and functional analysis as well as using genetically modified mice, we demonstrate that formation of antibacterial EVs depends upon stimulation of the multifunctional Mac-1 integrin complex, also called as complement receptor 3 (CR3), whereas activation of immunoglobulin binding Fc receptors or pattern recognition receptors alone or in combination is ineffective. Mac-1/CR3 stimulation and downstream tyrosine kinase signalling affect both the numbers, the cargo content and the antibacterial capacity of the produced vesicles. In contrast, Mac-1/CR3 signalling is not required for spontaneous EV formation, clearly indicating the existence of separate molecular pathways in EV biogenesis. We propose that EVs are "tailor-made" with different composition and functional properties depending on the environmental circumstances.