TY - JOUR
T1 - Neutrophil-derived extracellular vesicles modulate the phenotype of naïve human neutrophils
AU - Amjadi, Maya F.
AU - Avner, Benjamin S.
AU - Greenlee-Wacker, Mallary C.
AU - Horswill, Alexander R.
AU - Nauseef, William M.
N1 - Funding Information:
We recognize the assistance of members of the Iowa Inflammation Program including Kevin Leidal, Athmane Teghanemt, Sally McCormick-Hill, Priya Issuree, Silvie Kremserova, and Lauren Kinkead, as well as from the Edwina Rose Allen (Central Michigan University). This work was supported by National Institutes of Health (NIH) training grant 5T32AU996343 (B.S.A.), the Iowa Biosciences Academy (M.F.A.), the Iowa Center for Research by Undergraduates (M.F.A.), the Dewey Stuit Fund for Undergraduate Research (M.F.A.), NIH grants AI132335 and AI116546 (W.M.N.), NIH grant R15GM132992 (M.C.G-W.), Veterans Affairs Merit Review awards BX000513-09 (W.M.N.) and BX002711 (A.R.H.), and use of facilities at the Iowa City Department of Veterans Affairs Medical Center, Iowa City (IA, USA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2021 Society for Leukocyte Biology
PY - 2021/11
Y1 - 2021/11
N2 - Neutrophils (PMN) regulate inflammation in many ways, including communication with other immune cells via extracellular vesicles (EVs). EVs released by human neutrophils activated with N-formylmethionyl-leucyl-phenylalanine (fMLF) (PMN-fMLF EVs) had an outside-out orientation and contained functionally important neutrophil plasma membrane proteins, including flavocytochrome b558, and enzymatically active granule proteins, elastase, and myeloperoxidase. Treatment of naïve PMN with PMN-fMLF EVs primed fMLF-stimulated NADPH oxidase activity, increased surface expression of the complement receptors CD11b/CD18 and CD35, the specific granule membrane protein CD66, and flavocytochrome b558, and promoted phagocytosis of serum-opsonized Staphylococcus aureus. The primed oxidase activity reflected increased surface expression of flavocytochrome b558 and phosphorylation of SER345 in p47phox, two recognized mechanisms for oxidase priming. Taken together, these data demonstrate that stimulated PMN released EVs that altered the phenotype of naïve phagocytes by priming of the NADPH oxidase activity and augmenting phagocytosis, two responses that are integral to optimal PMN host defense.
AB - Neutrophils (PMN) regulate inflammation in many ways, including communication with other immune cells via extracellular vesicles (EVs). EVs released by human neutrophils activated with N-formylmethionyl-leucyl-phenylalanine (fMLF) (PMN-fMLF EVs) had an outside-out orientation and contained functionally important neutrophil plasma membrane proteins, including flavocytochrome b558, and enzymatically active granule proteins, elastase, and myeloperoxidase. Treatment of naïve PMN with PMN-fMLF EVs primed fMLF-stimulated NADPH oxidase activity, increased surface expression of the complement receptors CD11b/CD18 and CD35, the specific granule membrane protein CD66, and flavocytochrome b558, and promoted phagocytosis of serum-opsonized Staphylococcus aureus. The primed oxidase activity reflected increased surface expression of flavocytochrome b558 and phosphorylation of SER345 in p47phox, two recognized mechanisms for oxidase priming. Taken together, these data demonstrate that stimulated PMN released EVs that altered the phenotype of naïve phagocytes by priming of the NADPH oxidase activity and augmenting phagocytosis, two responses that are integral to optimal PMN host defense.
KW - Inflammation
KW - NADPH oxidase
KW - ectosomes
KW - microparticles
KW - phagocytosis
KW - priming
UR - http://www.scopus.com/inward/record.url?scp=85102196604&partnerID=8YFLogxK
U2 - 10.1002/JLB.3AB0520-339RR
DO - 10.1002/JLB.3AB0520-339RR
M3 - Article
AN - SCOPUS:85102196604
VL - 110
SP - 917
EP - 925
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 5
ER -