Purchase this article with an account.
Yutaka Sakurai, Masataka Ito, Yoko Karasawa, Masaru Takeuchi; Analysis of complement pathway in dacryoadenitis of programmed cell death-1 deficient mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4925.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Multiple studies have shown that unexplained low levels of complement component C3 of patients with Sjogren’s syndrome (SjS) are associated with high risk of disease severity and serious complication as a lymphoproliferative disease, non-Hodgkin lymphoma. It is considered that disturbed complement regulation may contribute to pathogenicity in SjS. Additionally, in the SjS model mouse, interfere with activity of complement resulted in inhibition of onset and development of SjS-like disease. The complement system is activated via three biochemical pathways: the classical complement pathway, the alternative complement pathway, and the lectin pathway. We reported that SjS-like dacryoadenitis and sialoadenitis were spontaneously induced in programmed cell death-1 deficient (PD-1 KO) mice. Three months-old PD-1 KO mice demonstrated lymphocytic infiltration in lacrimal gland (LG). We analized which of the complement pathways do activate in dacryoadenitis of PD-1 KO mice.
Total LG RNA and first-strand cDNA from PD-1 KO mice and wild type mice at 2, 3, 4 months of age were prepared. Relative expression of genes of C3, C1q (classical pathway), complement factor B (alternative pathway), and MASP-2 (lectin pathway) in LGs were analyzed by quantitative real-time PCR. Protein expression of Complement factor B (CFB) in LGs of PD-1 KO mice and wild type mice were analized by immunohistochemistry.
In LGs of 2 and 4 months-old PD-1 KO and WT mice, there were no significant differences in the gene expression of C3, C1q, and CFB, while at 3 months-old the gene expression of CFB in LGs of PD-1 KO mice were significantly higher than wild type mice. MASP-2 transcripts were not detected in LGs at 2, 3, 4 months-old in both PD-1 KO and WT mice. The CFB protein expression was seen in the lacrimal gland acinis and ducts of PD-1 KO mice at 3 months old by immunohistochemistry.
The results suggest that the activation of alternative complement pathway may be involved in SjS-like dacryoadenitis in PD-1 KO mice at initiation phase.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only