scholarly journals Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices

2021 ◽  
Vol 12 ◽  
Author(s):  
Sinan Muldur ◽  
Douangsone D. Vadysirisack ◽  
Sharan Ragunathan ◽  
Yalan Tang ◽  
Alonso Ricardo ◽  
...  
Keyword(s):  
Complement Activation ◽  
Ex Vivo ◽  
Human Neutrophils ◽  
Complement Factor ◽  
C5a Receptor ◽  
Cellular Immune Responses ◽  
Immunological Diseases ◽  
Microfluidic Assays ◽  
Cellular Immune ◽  
Potential Complement

Complement activation is key to anti-microbial defenses by directly acting on microbes and indirectly by triggering cellular immune responses. Complement activation may also contribute to the pathogenesis of numerous inflammatory and immunological diseases. Consequently, intense research focuses on developing therapeutics that block pathology-causing complement activation while preserving anti-microbial complement activities. However, the pace of research is slowed down significantly by the limitations of current tools for evaluating complement-targeting therapeutics. Moreover, the effects of potential therapeutic agents on innate immune cells, like neutrophils, are not fully understood. Here, we employ microfluidic assays and measure chemotaxis, phagocytosis, and swarming changes in human neutrophils ex vivo in response to various complement-targeting agents. We show that whereas complement factor 5 (C5) cleavage inhibitor eculizumab blocks all neutrophil anti-microbial functions, newer compounds like the C5 cleavage inhibitor RA101295 and C5a receptor antagonist avacopan inhibit chemotaxis and swarming while preserving neutrophil phagocytosis. These results highlight the utility of microfluidic neutrophil assays in evaluating potential complement-targeting therapeutics.

scholarly journals Intrarectal Immunization with Rotavirus 2/6 Virus-Like Particles Induces an Antirotavirus Immune Response Localized in the Intestinal Mucosa and Protects against Rotavirus Infection in Mice

2006 ◽  
Vol 80 (8) ◽  
pp. 3823-3832 ◽  
Author(s):  
Davide Agnello ◽  
Christine A. Hervé ◽  
Amandine Lavaux ◽  
Magali Darniot ◽  
Patrice Guillon ◽  
...  
Keyword(s):  
Immune Response ◽  
Intestinal Mucosa ◽  
Protective Immunity ◽  
Ex Vivo ◽  
Cellular Immune Responses ◽  
Adult Mice ◽  
Specific Immunoglobulin ◽  
Severe Gastroenteritis ◽  
Iga Production ◽  
Cellular Immune

ABSTRACT Rotavirus (RV) is the main etiological agent of severe gastroenteritis in infants, and vaccination seems the most effective way to control the disease. Recombinant rotavirus-like particles composed of the viral protein 6 (VP6) and VP2 (2/6-VLPs) have been reported to induce protective immunity in mice when administered by the intranasal (i.n.) route. In this study, we show that administration of 2/6-VLPs by the intrarectal (i.r.) route together with either cholera toxin (CT) or a CpG-containing oligodeoxynucleotide as the adjuvant protects adult mice against RV infection. Moreover, when CT is used, RV shedding in animals immunized by the i.r. route is even reduced in comparison with that in animals immunized by the i.n. route. Humoral and cellular immune responses induced by these immunization protocols were analyzed. We found that although i.r. immunization with 2/6-VLPs induces lower RV-specific immunoglobulin G (IgG) and IgA levels in serum, intestinal anti-RV IgA production is higher in mice immunized by the i.r. route. Cellular immune response has been evaluated by measuring cytokine production by spleen and Peyer's patch cells (PPs) after ex vivo restimulation with RV. Mice immunized by the i.n. and i.r. routes display higher gamma interferon production in spleen and PPs, respectively. In conclusion, we demonstrate that i.r. immunization with 2/6-VLPs protects against RV infection in mice and is more efficient than i.n. immunization in inducing an anti-RV immune response in intestinal mucosa.

The Roles of Complement Factor C5a and CINC-1 in Glucose Transport, Ultrafiltration, and Neutrophil Recruitment during Peritoneal Dialysis

2006 ◽  
Vol 26 (6) ◽  
pp. 688-696 ◽  
Author(s):  
Farhan Bazargani ◽  
Russell P. Rother ◽  
Magnus Braide
Keyword(s):  
Peritoneal Dialysis ◽  
Glucose Transport ◽  
Complement Activation ◽  
Ex Vivo ◽  
Neutrophil Recruitment ◽  
Coagulation System ◽  
Complement Factor ◽  
Indwelling Catheter ◽  
Recent Experimental Study ◽  
Ultra Filtration

Background In a recent experimental study, we showed that low molecular weight heparin improved ultrafiltration and blocked complement activation and coagulation in a single peritoneal dialysis (PD) dwell. Objective The aim of the present study was to evaluate the possible contribution of the complement factor C5a and the potential interactions between C5a, the coagulation system, and cytokines of the interleukin (IL)-8 family (cytokine-induced neutrophil chemoattractant; CINC-1). Methods Nonuremic rats were exposed through an indwelling catheter to a single dose of 20 mL glucose- (2.5%) based filter-sterilized PD fluid, with or without the addition of anti-rat C5 antibody. The dwell fluid was analyzed 2 and 4 hours later concerning activation of the coagulation cascades, neutrophil recruitment, ultrafiltration volume; CINC-1, glucose, urea, and histamine concentrations; and ex vivo intraperitoneal chemotactic activity. Results The numbers of neutrophils and levels of thrombin–antithrombin complex (TAT) and CINC-1 increased significantly during the PD dwell. C5 blockade significantly reduced the levels of TAT and increased the ultrafiltration volumes at 2 hours. Glucose concentrations were significantly positively correlated to ultrafiltration volumes. Conclusions Blockade of C5 leads to an increase in ultra-filtration, probably by a mechanism that involves a reduction in glucose transport. This effect may form a basis for improving PD efficiency in situations where high glucose transport limits ultrafiltration. Mechanisms connected to complement activation during PD may involve coagulation. Further studies of the intraperitoneal cascade systems under conditions of PD are indicated.

scholarly journals Complement Factor C5a Inhibits Apoptosis of Neutrophils—A Mechanism in Polytrauma?

2021 ◽  
Vol 10 (14) ◽  
pp. 3157
Author(s):  
Christian Ehrnthaller ◽  
Sonja Braumüller ◽  
Stephanie Kellermann ◽  
Florian Gebhard ◽  
Mario Perl ◽  
...  
Keyword(s):  
Complement Activation ◽  
Time Course ◽  
Fas Ligand ◽  
Polymorphonuclear Neutrophils ◽  
Complement Factor ◽  
Apoptotic Pathway ◽  
C5a Receptor ◽  
Reverse Complement ◽  
Polytrauma Patients

Life-threatening polytrauma results in early activation of the complement and apoptotic system, as well as leukocytes, ultimately leading to the clearance of damaged cells. However, little is known about interactions between the complement and apoptotic systems in PMN (polymorphonuclear neutrophils) after multiple injuries. PMN from polytrauma patients and healthy volunteers were obtained and assessed for apoptotic events along the post-traumatic time course. In vitro studies simulated complement activation by the exposure of PMN to C3a or C5a and addressed both the intrinsic and extrinsic apoptotic pathway. Specific blockade of the C5a-receptor 1 (C5aR1) on PMN was evaluated for efficacy to reverse complement-driven alterations. PMN from polytrauma patients exhibited significantly reduced apoptotic rates up to 10 days post trauma compared to healthy controls. Polytrauma-induced resistance was associated with significantly reduced Fas-ligand (FasL) and Fas-receptor (FasR) on PMN and in contrast, significantly enhanced FasL and FasR in serum. Simulation of systemic complement activation revealed for C5a, but not for C3a, a dose-dependent abrogation of PMN apoptosis in both intrinsic and extrinsic pathways. Furthermore, specific blockade of the C5aR1 reversed C5a-induced PMN resistance to apoptosis. The data suggest an important regulatory and putative mechanistic and therapeutic role of the C5a/C5aR1 interaction on PMN apoptosis after polytrauma.

scholarly journals Microfluidic Assays for Probing Neutrophil-Borrelia Interactions in Blood During Lyme Disease

2021 ◽  
pp. 1-11
Author(s):  
Sinan Muldur ◽  
Felix Ellett ◽  
Anika L. Marand ◽  
Charles Marvil ◽  
John A. Branda ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Human Neutrophils ◽  
Complement Factor ◽  
Complement Receptors ◽  
Blood Samples ◽  
Spontaneous Motility ◽  
Healthy Donors ◽  
Highly Sensitive ◽  
Microfluidic Assays

Human neutrophils are highly sensitive to the presence of Borrelia burgdorferi (Bb), the agent of Lyme disease (LD), in tissues. Although Bb is also found in the blood of LD patients, far less is known about how neutrophils respond to Bb in the presence of blood. In this study, we employed microfluidic tools to probe the interaction between human neutrophils and Bb and measured the activation of human neutrophils in blood samples from patients. We found that neutrophils migrate vigorously toward Bb in the presence of serum, and this process was complement-dependent. Preventing complement factor 5 cleavage or blocking complement receptors decreased neutrophil’s ability to interact with Bb. We also found that spiking Bb directly into the blood from healthy donors induced spontaneous neutrophil motility. This response to Bb was also complement-dependent. Preventing complement factor 5 cleavage decreased spontaneous neutrophil motility in Bb-spiked blood. Moreover, we found that neutrophils in blood samples from acute LD patients displayed spontaneous motility patterns similar to those observed in Bb-spiked samples. Neutrophil motility was more robust in blood samples from LD patients than that measured in healthy and ill controls, validating the utility of the microfluidic assay for the study of neutrophil-Bb interactions in the presence of blood.

Effect of congestive heart failure on humoral and ex vivo cellular immune responses to influenza vaccination in older adults

Vaccine ◽  
2004 ◽  
Vol 22 (5-6) ◽  
pp. 681-688 ◽  
Author(s):  
Janet E. McElhaney ◽  
John M. Herre ◽  
M.Louise Lawson ◽  
Sharon K. Cole ◽  
Bonnie L. Burke ◽  
...  
Keyword(s):  
Heart Failure ◽  
Older Adults ◽  
Congestive Heart Failure ◽  
Immune Responses ◽  
Influenza Vaccination ◽  
Ex Vivo ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Assessment of the potential of a boron–fructose additive in counteracting the toxic effect of Fusarium mycotoxins

2011 ◽  
Vol 106 (3) ◽  
pp. 398-407 ◽  
Author(s):  
Ionelia Taranu ◽  
Daniela E. Marin ◽  
Gina Manda ◽  
Monica Motiu ◽  
Ionela Neagoe ◽  
...  
Keyword(s):  
Immune Response ◽  
Ex Vivo ◽  
Fusarium Mycotoxins ◽  
Feeding Trial ◽  
Peripheral Blood Mononuclear ◽  
Cellular Immune Responses ◽  
Tnf Α ◽  
Soyabean Meal ◽  
Calcium Fructoborate ◽  
Cellular Immune

Trichotecenes are mycotoxins produced by Fusarium sp., which may contaminate animal feeds and human food. A feeding trial was conducted to evaluate the effect of a fusarotoxin-contaminated diet, and to explore the counteracting potential of a calcium fructoborate (CFrB) additive on performance, typical health biochemistry parameters and immune response in weaned pigs. A naturally contaminated maize, containing low doses of deoxynivalenol, zearalenone, fumonisins and T-2/HT-2 toxins (1790, 20, 0·6 and 90 parts per billion), was included in a maize–soyabean meal diet, and given ad libitum to eight weaned piglets (two groups: four pigs/group) for a period of 24 d. CFrB was administered to one of the contaminated groups and to another four piglets as a daily supplement, following the manufacturer's recommendation. A decrease in performance was observed in contaminated animals at this concentration of feed toxins, which was ameliorated by the dietary CFrB supplementation. Fusarium toxins also altered the pig immune response by increasing (P < 0·05) the ex vivo peripheral blood mononuclear cell proliferation (111·7 % in comparison with control), the respiratory burst of porcine granulocytes (15·4 % for responsive cells v. 5·1 % for unstimulated cells and 70·95 v. 22·65 % for stimulated cells, respectively), the percentage of peripheral T, CD3+, CD3+CD4+ and CD3+CD8+ subsets and the synthesis of IL-1β, TNF-α and IL-8 (123·8, 217·1 and 255·1 %, respectively). The diet containing the CFrB additive reduced these exacerbated cellular immune responses induced by Fusarium toxins. However, consumption of CFrB did not counteract the effect of mycotoxins on biochemistry parameters, and increased plasma IgM and IgG of contaminated pigs.

Sign in / Sign up

Export Citation Format

Share Document