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Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions

Besides being a key effector arm of innate immunity, a plethora of non-canonical functions of complement has recently been emerging. Factor H (FH), the main regulator of the alternative pathway of complement activation, has been reported to bind to various immune cells and regulate their functions,...

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Autores principales: Kárpáti, Éva, Kremlitzka, Mariann, Sándor, Noémi, Hajnal, Dávid, Schneider, Andrea E., Józsi, Mihály
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521052/
https://www.ncbi.nlm.nih.gov/pubmed/34671340
http://dx.doi.org/10.3389/fimmu.2021.660852
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author Kárpáti, Éva
Kremlitzka, Mariann
Sándor, Noémi
Hajnal, Dávid
Schneider, Andrea E.
Józsi, Mihály
author_facet Kárpáti, Éva
Kremlitzka, Mariann
Sándor, Noémi
Hajnal, Dávid
Schneider, Andrea E.
Józsi, Mihály
author_sort Kárpáti, Éva
collection PubMed
description Besides being a key effector arm of innate immunity, a plethora of non-canonical functions of complement has recently been emerging. Factor H (FH), the main regulator of the alternative pathway of complement activation, has been reported to bind to various immune cells and regulate their functions, beyond its role in modulating complement activation. In this study we investigated the effect of FH, its alternative splice product FH-like protein 1 (FHL-1), the FH-related (FHR) proteins FHR-1 and FHR-5, and the recently developed artificial complement inhibitor mini-FH, on two key innate immune cells, monocytes and neutrophilic granulocytes. We found that, similar to FH, the other factor H family proteins FHL-1, FHR-1 and FHR-5, as well as the recombinant mini-FH, are able to bind to both monocytes and neutrophils. As a functional outcome, immobilized FH and FHR-1 inhibited PMA-induced NET formation, but increased the adherence and IL-8 production of neutrophils. FHL-1 increased only the adherence of the cells, while FHR-5 was ineffective in altering these functions. The adherence of monocytes was increased on FH, recombinant mini-FH and FHL-1 covered surfaces and, except for FHL-1, the same molecules also enhanced secretion of the inflammatory cytokines IL-1β and TNFα. When monocytes were stimulated with LPS in the presence of immobilized FH family proteins, FH, FHL-1 and mini-FH enhanced whereas FHR-1 and FHR-5 decreased the secretion of TNFα; FHL-1 and mini-FH also enhanced IL-10 release compared to the effect of LPS alone. Our results reveal heterogeneous effects of FH and FH family members on monocytes and neutrophils, altering key features involved in pathogen killing, and also demonstrate that FH-based complement inhibitors, such as mini-FH, may have effects beyond their function of inhibiting complement activation. Thus, our data provide new insight into the non-canonical functions of FH, FHL-1, FHR-1 and FHR-5 that might be exploited during protection against infections and in vaccine development.
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spelling pubmed-85210522021-10-19 Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions Kárpáti, Éva Kremlitzka, Mariann Sándor, Noémi Hajnal, Dávid Schneider, Andrea E. Józsi, Mihály Front Immunol Immunology Besides being a key effector arm of innate immunity, a plethora of non-canonical functions of complement has recently been emerging. Factor H (FH), the main regulator of the alternative pathway of complement activation, has been reported to bind to various immune cells and regulate their functions, beyond its role in modulating complement activation. In this study we investigated the effect of FH, its alternative splice product FH-like protein 1 (FHL-1), the FH-related (FHR) proteins FHR-1 and FHR-5, and the recently developed artificial complement inhibitor mini-FH, on two key innate immune cells, monocytes and neutrophilic granulocytes. We found that, similar to FH, the other factor H family proteins FHL-1, FHR-1 and FHR-5, as well as the recombinant mini-FH, are able to bind to both monocytes and neutrophils. As a functional outcome, immobilized FH and FHR-1 inhibited PMA-induced NET formation, but increased the adherence and IL-8 production of neutrophils. FHL-1 increased only the adherence of the cells, while FHR-5 was ineffective in altering these functions. The adherence of monocytes was increased on FH, recombinant mini-FH and FHL-1 covered surfaces and, except for FHL-1, the same molecules also enhanced secretion of the inflammatory cytokines IL-1β and TNFα. When monocytes were stimulated with LPS in the presence of immobilized FH family proteins, FH, FHL-1 and mini-FH enhanced whereas FHR-1 and FHR-5 decreased the secretion of TNFα; FHL-1 and mini-FH also enhanced IL-10 release compared to the effect of LPS alone. Our results reveal heterogeneous effects of FH and FH family members on monocytes and neutrophils, altering key features involved in pathogen killing, and also demonstrate that FH-based complement inhibitors, such as mini-FH, may have effects beyond their function of inhibiting complement activation. Thus, our data provide new insight into the non-canonical functions of FH, FHL-1, FHR-1 and FHR-5 that might be exploited during protection against infections and in vaccine development. Frontiers Media S.A. 2021-10-04 /pmc/articles/PMC8521052/ /pubmed/34671340 http://dx.doi.org/10.3389/fimmu.2021.660852 Text en Copyright © 2021 Kárpáti, Kremlitzka, Sándor, Hajnal, Schneider and Józsi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Kárpáti, Éva
Kremlitzka, Mariann
Sándor, Noémi
Hajnal, Dávid
Schneider, Andrea E.
Józsi, Mihály
Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions
title Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions
title_full Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions
title_fullStr Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions
title_full_unstemmed Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions
title_short Complement Factor H Family Proteins Modulate Monocyte and Neutrophil Granulocyte Functions
title_sort complement factor h family proteins modulate monocyte and neutrophil granulocyte functions
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521052/
https://www.ncbi.nlm.nih.gov/pubmed/34671340
http://dx.doi.org/10.3389/fimmu.2021.660852
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