Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells Via C1q and C3a Synthesis

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2017 Jul 9

PMID 28687659

Citations 21

Authors

Mitra J Hooshmand

Hal X Nguyen

Katja M Piltti

Francisca Benavente

Samuel Hong

Lisa Flanagan

Nobuko Uchida

Brian J Cummings

Aileen J Anderson

Affiliations

Soon will be listed here.

Abstract

Inflammatory processes play a key role in pathophysiology of many neurologic diseases/trauma, but the effect of immune cells and factors on neurotransplantation strategies remains unclear. We hypothesized that cellular and humoral components of innate immunity alter fate and migration of human neural stem cells (hNSC). In these experiments, conditioned media collected from polymorphonuclear leukocytes (PMN) selectively increased hNSC astrogliogenesis and promoted cell migration in vitro. PMN were shown to generate C1q and C3a; exposure of hNSC to PMN-synthesized concentrations of these complement proteins promoted astrogliogenesis and cell migration. Furthermore, in vitro, Abs directed against C1q and C3a reversed the fate and migration effects observed. In a proof-of-concept in vivo experiment, blockade of C1q and C3a transiently altered hNSC migration and reversed astroglial fate after spinal cord injury. Collectively, these data suggest that modulation of the innate/humoral inflammatory microenvironment may impact the potential of cell-based therapies for recovery and repair following CNS pathology.

Citing Articles

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References

Bentley C, Fries W, Brade V . Synthesis of factors D, B and P of the alternative pathway of complement activation, as well as of C3, by guinea-pig peritoneal macrophages in vitro. Immunology. 1978; 35(6):971-80. PMC: 1457427. View

Shihabuddin L, Horner P, Ray J, Gage F . Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J Neurosci. 2000; 20(23):8727-35. PMC: 6773057. View

Uchida N, Buck D, He D, Reitsma M, Masek M, Phan T . Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A. 2000; 97(26):14720-5. PMC: 18985. DOI: 10.1073/pnas.97.26.14720. View

Venge P, Olsson I . Cationic proteins of human granulocytes. VI. Effects on the complement system and mediation of chemotactic activity. J Immunol. 1975; 115(6):1505-8. View

Tamaki S, Eckert K, He D, Sutton R, Doshe M, Jain G . Engraftment of sorted/expanded human central nervous system stem cells from fetal brain. J Neurosci Res. 2002; 69(6):976-86. DOI: 10.1002/jnr.10412. View

Arnett H, Wang Y, Matsushima G, Suzuki K, Ting J . Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. J Neurosci. 2003; 23(30):9824-32. PMC: 6740899. View

Monje M, Toda H, Palmer T . Inflammatory blockade restores adult hippocampal neurogenesis. Science. 2003; 302(5651):1760-5. DOI: 10.1126/science.1088417. View

Ben-Hur T, Ben-Menachem O, Furer V, Einstein O, Mizrachi-Kol R, Grigoriadis N . Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells. Mol Cell Neurosci. 2003; 24(3):623-31. DOI: 10.1016/s1044-7431(03)00218-5. View

Aarum J, Sandberg K, Budd Haeberlein S, Persson M . Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci U S A. 2003; 100(26):15983-8. PMC: 307679. DOI: 10.1073/pnas.2237050100. View

10.

Botto M, Lissandrini D, Sorio C, Walport M . Biosynthesis and secretion of complement component (C3) by activated human polymorphonuclear leukocytes. J Immunol. 1992; 149(4):1348-55. View

11.

Rot A, von Andrian U . Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol. 2004; 22:891-928. DOI: 10.1146/annurev.immunol.22.012703.104543. View

12.

Wurmser A, Palmer T, Gage F . Neuroscience. Cellular interactions in the stem cell niche. Science. 2004; 304(5675):1253-5. DOI: 10.1126/science.1099344. View

13.

Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M . The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004; 25(12):677-86. DOI: 10.1016/j.it.2004.09.015. View

14.

Imitola J, Raddassi K, Park K, Mueller F, Nieto M, Teng Y . Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A. 2004; 101(52):18117-22. PMC: 536055. DOI: 10.1073/pnas.0408258102. View

15.

Anderson A, Robert S, Huang W, Young W, Cotman C . Activation of complement pathways after contusion-induced spinal cord injury. J Neurotrauma. 2005; 21(12):1831-46. DOI: 10.1089/neu.2004.21.1831. View

16.

JONES T, McDaniel E, Popovich P . Inflammatory-mediated injury and repair in the traumatically injured spinal cord. Curr Pharm Des. 2005; 11(10):1223-36. DOI: 10.2174/1381612053507468. View

17.

Pluchino S, Zanotti L, Rossi B, Brambilla E, Ottoboni L, Salani G . Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature. 2005; 436(7048):266-71. DOI: 10.1038/nature03889. View

18.

Vianello F, Olszak I, Poznansky M . Fugetaxis: active movement of leukocytes away from a chemokinetic agent. J Mol Med (Berl). 2005; 83(10):752-63. DOI: 10.1007/s00109-005-0675-z. View

19.

Cummings B, Uchida N, Tamaki S, Salazar D, Hooshmand M, Summers R . Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proc Natl Acad Sci U S A. 2005; 102(39):14069-74. PMC: 1216836. DOI: 10.1073/pnas.0507063102. View

20.

Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar A, Pluchino S . Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci. 2005; 31(1):149-60. DOI: 10.1016/j.mcn.2005.10.006. View