Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants

Giacomo Gravina; Maryam Ardalan; Tetyana Chumak; Anders K Nilsson; Joakim C Ek; Hanna Danielsson; Pernilla Svedin; Milos Pekny; Marcela Pekna; Karin Sävman; Ann Hellström; Carina Mallard

doi:10.1016/j.isci.2023.107217

Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants

iScience. 2023 Jun 27;26(7):107217. doi: 10.1016/j.isci.2023.107217. eCollection 2023 Jul 21.

Authors

Giacomo Gravina¹, Maryam Ardalan^{1

2}, Tetyana Chumak¹, Anders K Nilsson³, Joakim C Ek¹, Hanna Danielsson^{4

5}, Pernilla Svedin¹, Milos Pekny^{6

7

8}, Marcela Pekna^{7

8

9}, Karin Sävman^{10

11}, Ann Hellström³, Carina Mallard¹

Affiliations

¹ Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Translational Neuropsychiatric Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
³ Section for Ophthalmology, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
⁵ Sach's Children's and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
⁶ Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁷ University of Newcastle, Newcastle, NSW, Australia.
⁸ Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
⁹ Laboratory of Regenerative Neurobiology, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
¹⁰ Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
¹¹ Region Västra Götaland, Department of Neonatology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract

Staphylococcus (S.) epidermidis is the most common nosocomial coagulase-negative staphylococci infection in preterm infants. Clinical signs of infection are often unspecific and novel markers to complement diagnosis are needed. We investigated proteomic alterations in mouse brain after S. epidermidis infection and in preterm infant blood. We identified lipocalin-2 (LCN2) as a crucial protein associated with cerebrovascular changes and astrocyte reactivity in mice. We further proved that LCN2 protein expression was associated with endothelial cells but not astrocyte reactivity. By combining network analysis and differential expression approaches, we identified LCN2 linked to blood C-reactive protein levels in preterm infants born <28 weeks of gestation. Blood LCN2 levels were associated with similar alterations of cytokines and chemokines in both infected mice and human preterm infants with increased levels of C-reactive protein. This experimental and clinical study suggests that LCN2 may be a marker of preterm infection/inflammation associated with cerebrovascular changes and neuroinflammation.

Keywords: Immunology; Neurology; Proteomics.