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Neutrophils interact with adenovirus vectors via Fc receptors and complement receptor 1.
J Virol. 2005 Dec; 79(23):14622-31.JV

Abstract

Neutrophils are effectors of the innate immune response to adenovirus vectors. Following the systemic administration of Cy2-labeled AdLuc in mice, flow cytometry and PCR analysis of liver leukocytes revealed that 25% of recruited neutrophils interacted with adenovirus vectors. In vitro, flow cytometry of human neutrophils incubated with Cy2-labeled AdLuc also demonstrated a significant interaction with adenovirus vectors. Fluorescence and electron microscopy confirmed vector internalization by neutrophils. The AdLuc-neutrophil interaction reduced vector transduction efficiency by more than 50% in coincubation assays in epithelium-derived cells. Adenovirus vector uptake by neutrophils occurred independently of coxsackievirus adenovirus receptor (CAR) and capsid RGD motifs, since neutrophils do not express CAR and uptake of the RGD-deleted vector AdL.PB* was similar to that of AdLuc. Furthermore, both AdLuc and AdL.PB* activated neutrophils and induced similar degrees of L-selectin shedding. Neutrophil uptake of AdLuc was dependent on the presence of complement and antibodies, since the interaction between AdLuc and neutrophils was significantly reduced when they were incubated in immunoglobulin G-depleted or heat-inactivated human serum. Blocking of complement receptor 1 (CD35) but not complement receptor 3 (CD11b/CD18) significantly reduced neutrophil uptake of AdLuc. Blocking of Fc gammaRI (CD64), Fc gammaRII (CD32), and Fc gammaRIII (CD16) individually or together also reduced neutrophil uptake of AdLuc, although less than blocking of CD35 alone. Combined CR1 and Fc receptor blockade synergistically inhibited neutrophil-AdLuc interactions close to baseline. These results demonstrate opsonin-dependent adenovirus vector interactions with neutrophils and their corresponding receptors.

Authors+Show Affiliations

Department of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16282462

Citation

Cotter, Matthew J., et al. "Neutrophils Interact With Adenovirus Vectors Via Fc Receptors and Complement Receptor 1." Journal of Virology, vol. 79, no. 23, 2005, pp. 14622-31.
Cotter MJ, Zaiss AK, Muruve DA. Neutrophils interact with adenovirus vectors via Fc receptors and complement receptor 1. J Virol. 2005;79(23):14622-31.
Cotter, M. J., Zaiss, A. K., & Muruve, D. A. (2005). Neutrophils interact with adenovirus vectors via Fc receptors and complement receptor 1. Journal of Virology, 79(23), 14622-31.
Cotter MJ, Zaiss AK, Muruve DA. Neutrophils Interact With Adenovirus Vectors Via Fc Receptors and Complement Receptor 1. J Virol. 2005;79(23):14622-31. PubMed PMID: 16282462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neutrophils interact with adenovirus vectors via Fc receptors and complement receptor 1. AU - Cotter,Matthew J, AU - Zaiss,Anne K, AU - Muruve,Daniel A, PY - 2005/11/12/pubmed PY - 2006/1/24/medline PY - 2005/11/12/entrez SP - 14622 EP - 31 JF - Journal of virology JO - J Virol VL - 79 IS - 23 N2 - Neutrophils are effectors of the innate immune response to adenovirus vectors. Following the systemic administration of Cy2-labeled AdLuc in mice, flow cytometry and PCR analysis of liver leukocytes revealed that 25% of recruited neutrophils interacted with adenovirus vectors. In vitro, flow cytometry of human neutrophils incubated with Cy2-labeled AdLuc also demonstrated a significant interaction with adenovirus vectors. Fluorescence and electron microscopy confirmed vector internalization by neutrophils. The AdLuc-neutrophil interaction reduced vector transduction efficiency by more than 50% in coincubation assays in epithelium-derived cells. Adenovirus vector uptake by neutrophils occurred independently of coxsackievirus adenovirus receptor (CAR) and capsid RGD motifs, since neutrophils do not express CAR and uptake of the RGD-deleted vector AdL.PB* was similar to that of AdLuc. Furthermore, both AdLuc and AdL.PB* activated neutrophils and induced similar degrees of L-selectin shedding. Neutrophil uptake of AdLuc was dependent on the presence of complement and antibodies, since the interaction between AdLuc and neutrophils was significantly reduced when they were incubated in immunoglobulin G-depleted or heat-inactivated human serum. Blocking of complement receptor 1 (CD35) but not complement receptor 3 (CD11b/CD18) significantly reduced neutrophil uptake of AdLuc. Blocking of Fc gammaRI (CD64), Fc gammaRII (CD32), and Fc gammaRIII (CD16) individually or together also reduced neutrophil uptake of AdLuc, although less than blocking of CD35 alone. Combined CR1 and Fc receptor blockade synergistically inhibited neutrophil-AdLuc interactions close to baseline. These results demonstrate opsonin-dependent adenovirus vector interactions with neutrophils and their corresponding receptors. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/16282462/Neutrophils_interact_with_adenovirus_vectors_via_Fc_receptors_and_complement_receptor_1_ L2 - https://journals.asm.org/doi/10.1128/JVI.79.23.14622-14631.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -