Open AccessAlbumin Nanoparticle Endocytosing Subset of Neutrophils for Precision Therapeutic Targeting of Inflammatory Tissue Injury
Author(s) -
Kurt Bachmaier,
Andrew Stuart,
Abhalaxmi Singh,
Asok Mukhopadhyay,
Sreeparna Chakraborty,
Zhigang Hong,
Li Wang,
Yoshikazu Tsukasaki,
Mark MaienscheinCline,
Balaji Ganesh,
Prasad Kanteti,
Jalees Rehman,
Asrar B. Malik
Publication year - 2022
Publication title -
acs nano
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.554
H-Index - 382
eISSN - 1936-086X
pISSN - 1936-0851
DOI - 10.1021/acsnano.1c09762
Subject(s) - syk , inflammation , chemokine , proinflammatory cytokine , immunology , population , biology , spleen , in vivo , microbiology and biotechnology , medicine , tyrosine kinase , signal transduction , environmental health
The complex involvement of neutrophils in inflammatory diseases makes them intriguing but challenging targets for therapeutic intervention. Here, we tested the hypothesis that varying endocytosis capacities would delineate functionally distinct neutrophil subpopulations that could be specifically targeted for therapeutic purposes. By using uniformly sized (∼120 nm in diameter) albumin nanoparticles (ANP) to characterize mouse neutrophils in vivo , we found two subsets of neutrophils, one that readily endocytosed ANP (ANP high neutrophils) and another that failed to endocytose ANP (ANP low population). These ANP high and ANP low subsets existed side by side simultaneously in bone marrow, peripheral blood, spleen, and lungs, both under basal conditions and after inflammatory challenge. Human peripheral blood neutrophils showed a similar duality. ANP high and ANP low neutrophils had distinct cell surface marker expression and transcriptomic profiles, both in naive mice and in mice after endotoxemic challenge. ANP high and ANP low neutrophils were functionally distinct in their capacities to kill bacteria and to produce inflammatory mediators. ANP high neutrophils produced inordinate amounts of reactive oxygen species and inflammatory chemokines and cytokines. Targeting this subset with ANP loaded with the drug piceatannol, a spleen tyrosine kinase (Syk) inhibitor, mitigated the effects of polymicrobial sepsis by reducing tissue inflammation while fully preserving neutrophilic host-defense function.