Extremely high-frequency electromagnetic radiation enhances neutrophil response to particulate agonists.

The growing use of extremely high-frequency electromagnetic radiation (EHF EMR) in information and communication technology and in biomedical applications has raised concerns regarding the potential biological impact of millimeter waves (MMWs). Here, we elucidated the effects of MMW radiation on neutrophil activation induced by opsonized zymosan or E. coli in whole blood ex vivo. After agonist addition to blood, two samples were prepared. A control sample was incubated at ambient conditions without any treatment, and a test sample was exposed to EHF EMR (32.9-39.6 GHz, 100 W/m2 ). We used methods that allowed us to assess the functional status of neutrophils immediately after exposure: oxidant production levels were measured by luminol-dependent chemiluminescence, and morphofunctional changes to neutrophils were observed in blood smears. Results revealed that the response of neutrophils to both agonists was intensified if blood was exposed to MMW radiation for 15 min. Neutrophils were intact in both the control and irradiated samples if no agonist was added to blood before incubation. Similarly, exposing suspensions of isolated neutrophils in plasma to MMW radiation enhanced cell response to both zymosan and E. coli. Heating blood samples was shown to be the primary mechanism underlying enhanced EHF EMR-induced oxidant production by neutrophils in response to particulate agonists. Bioelectromagnetics. 39:144-155, 2018. © 2017 Wiley Periodicals, Inc.

Albumin reduces thrombogenic potential of single-walled carbon nanotubes.

Reduction of thrombogenicity of carbon nanotubes is an important prerequisite for their biomedical use. We assessed the thrombogenic activity of carboxylated single-walled carbon nanotubes (c-SWCNTs) and covalently PEGylated c-SWNCTs (PEG-SWCNTs) by testing the clotting time of platelet poor plasma and platelet aggregation in whole blood samples, and evaluated the impact of human serum albumin on thrombogenicity of carbon nanotubes. Both types of SWCNTs exhibited considerable thrombogenic activity. SWCNTs accelerated plasma clotting, with a lesser effect seen for PEG-SWCNTs. Treatment of SWCNTs with albumin did not affect the SWCNT-induced shortening of clotting time. In whole blood, no discernible differences in the effect of c-SWCNTs and PEG-SWCNTs on platelets were observed. Upon addition of SWCNTs to blood, dose- and time-dependent formation of agglomerates of nanotubes and platelets was demonstrated. Pretreatment of SWCNTs with albumin reduced the platelet aggregation: the number of single platelets increased, and the size of platelet-SWCNT agglomerates decreased dramatically. Hence, addition of albumin may serve to attenuate the adverse, thrombogenic effect of CNTs.

PEGylated single-walled carbon nanotubes activate neutrophils to increase production of hypochlorous acid, the oxidant capable of degrading nanotubes.

Perspectives for the use of carbon nanotubes in biomedical applications depend largely on their ability to degrade in the body into products that can be easily cleared out. Carboxylated single-walled carbon nanotubes (c-SWCNTs) were shown to be degraded by oxidants generated by peroxidases in the presence of hydrogen peroxide. In the present study we demonstrated that conjugation of poly(ethylene glycol) (PEG) to c-SWCNTs does not interfere with their degradation by peroxidase/H(2)O(2) system or by hypochlorite. Comparison of different heme-containing proteins for their ability to degrade PEG-SWCNTs has led us to conclude that the myeloperoxidase (MPO) product hypochlorous acid (HOCl) is the major oxidant that may be responsible for biodegradation of PEG-SWCNTs in vivo. MPO is secreted mainly by neutrophils upon activation. We hypothesize that SWCNTs may enhance neutrophil activation and therefore stimulate their own biodegradation due to MPO-generated HOCl. PEG-SWCNTs at concentrations similar to those commonly used in in vivo studies were found to activate isolated human neutrophils to produce HOCl. Both PEG-SWCNTs and c-SWCNTs enhanced HOCl generation from isolated neutrophils upon serum-opsonized zymosan stimulation. Both types of nanotubes were also found to activate neutrophils in whole blood samples. Intraperitoneal injection of a low dose of PEG-SWCNTs into mice induced an increase in percentage of circulating neutrophils and activation of neutrophils and macrophages in the peritoneal cavity, suggesting the evolution of an inflammatory response. Activated neutrophils can produce high local concentrations of HOCl, thereby creating the conditions favorable for degradation of the nanotubes.