Study of a novel neuraminidase 1 knockout mouse links the pathology of sialidosis in the nervous, renal and reproductive system

Kho, Ikhui; Pan, Xuefang; Cairo, Christopher W.; Morales, Carlos Matta; Pshezhetsky, Alexey V.

doi:10.1016/j.ymgme.2019.11.220

Cited by 2 publications

(3 citation statements)

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“…33 Signs of neuroinflammation including microastrogliosis and increased brain levels of MIP-1α (CCL3) have been also reported for Neu3 KO, Neu4 KO, and Neu3/Neu4 DKO mice, but the levels were substantially lower compared with Neu1 KO mice. 20,34 Thus, increased basal level inflammation in Neu 1 KO mice is in agreement with previous studies.…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies in human patients and mouse models of sialidosis have revealed that progressive neuroinflammation and leukocyte infiltration in peripheral tissues are hallmarks of this disease 33 . Signs of neuroinflammation including microastrogliosis and increased brain levels of MIP‐1α (CCL3) have been also reported for Neu3 KO, Neu4 KO, and Neu3 / Neu4 DKO mice, but the levels were substantially lower compared with Neu1 KO mice 20,34 …”

Section: Discussionmentioning

confidence: 98%

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The Janus‐like role of neuraminidase isoenzymes in inflammation

et al. 2022

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The processes of activation, extravasation, and migration of immune cells to a site are early and essential steps in the induction of an acute inflammatory response. These events are an essential part of the inflammatory cascade, which involves multiple regulatory steps. Using a murine air pouch model of inflammation with LPS as an inflammation inducer, we demonstrate that isoenzymes of the neuraminidase family (NEU1, 3, and 4) play essential roles in these processes by acting as positive or negative regulators of leukocyte infiltration. In genetically knocked‐out (KO) mice for different NEU genes (Neu1 KO, Neu3 KO, Neu4 KO, and Neu3/4 double KO mice) with LPS‐induced air pouch inflammation, leukocytes at the site of inflammation were counted, and the inflamed tissue was analyzed using immunohistochemistry. Our data show that leukocyte recruitment was decreased in NEU1‐ and NEU3‐deficient mice, while it was increased in NEU4‐deficient animals. Consistent with these results, systemic as well as pouch exudate levels of pro‐inflammatory cytokines were reduced in Neu1 and increased in Neu4 KO mice. Pharmacological inhibitors specific for NEU1, NEU3, and NEU4 isoforms also affected leukocyte recruitment. Together our data demonstrate that NEU isoenzymes have distinct—and even opposing—effects on leukocyte recruitment, and therefore warrant further investigation to determine their mechanisms and importance as regulators of the inflammatory cascade.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 98%

The Janus‐like role of neuraminidase isoenzymes in inflammation

et al. 2022

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“…(Wu et al, 2010) Signs of neuroinflammation including microastrogliosis and increased brain levels of MIP-1α (CCL3) have been also reported for Neu3 KO, Neu4 KO, and Neu3/Neu4 DKO mice but the levels were substantially lower as compared to Neu1 KO animals. (Kho et al, 2020;Pan et al, 2017) Because the results obtained in KO mice suggested that pharmacological inhibition of NEU1 and NEU3 could be used for manipulating the inflammatory response, we further tested if specific inhibitors of neuraminidases were able to modulate leukocyte recruitment in the air pouch model. The results of our experiments with an inhibitor of NEU1 (IN1) were not conclusive due to the high variability between animals.…”

Section: Discussionmentioning

confidence: 99%

The Janus-like role of neuraminidase isoenzymes in inflammation

Samarani

et al. 2021

Preprint

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The processes of activation, extravasation, and migration of immune cells to a site are early and essential steps in the induction of an acute inflammatory response. These events are part of the inflammatory cascade which involves multiple regulatory steps. Using a murine air-pouch model of inflammation with LPS as an inflammation inducer we demonstrate that isoenzymes of the neuraminidase family (NEU1, 3, and 4) play essential roles in this process acting as positive or negative regulators of leukocyte infiltration. Genetically knocked-out (KO) mice for different NEU genes (Neu1 KO, Neu3 KO, Neu4 KO, and Neu3/4 double KO mice) were induced with LPS, leukocytes at the site of inflammation were counted, and the inflamed tissue was analyzed using immunohistochemistry. Our data show that leukocyte recruitment was decreased in NEU1 and NEU3-deficient mice, while it was increased in NEU4-deficient animals. Consistent with these results, systemic levels of pro-inflammatory cytokines and those in pouch exudate were reduced in Neu1 and increased in Neu4 KO mice. We found that pharmacological inhibitors specific for NEU1, NEU3, and NEU4 isoforms also affected leukocyte recruitment. We conclude that NEU isoenzymes have distinct – and even opposing – effects on leukocyte recruitment, and therefore warrant further investigation to determine their mechanisms and importance as regulators of the inflammatory cascade.

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Study of a novel neuraminidase 1 knockout mouse links the pathology of sialidosis in the nervous, renal and reproductive system

Cited by 2 publications

References 0 publications

The Janus‐like role of neuraminidase isoenzymes in inflammation

The Janus‐like role of neuraminidase isoenzymes in inflammation

The Janus-like role of neuraminidase isoenzymes in inflammation

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