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R. W. Read, S. D. Vogt, S. R. Barnum; The Pro-Inflammatory Effects of Complement Activation in Experimental Autoimmune Uveitis Are Mediated by Neither Engagement of the Anaphylatoxin Receptors Individually Nor the Formation of the Membrane Attack Complex. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2642.
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To determine the downstream complement activation product or products responsible for the exacerbating effect on experimental autoimmune uveitis previously described.
C57BL/6 mice deficient in the receptor for the anaphylatoxin C3a or C5a (C3aR-KO and C5aR-KO, respectively) or mice deficient for C5 were induced for EAU with a peptide of amino acids 1-20 of human IRBP in complete Freund's adjuvant with concurrent pertussis toxin. Wild type animals were concurrently induced. Animals were sacrificed at 21 days following induction, their eyes enucleated and snap frozen in OCT. 10 micron sections were stained with H&E and 6 equidistant planes through the eye rated for the severity of EAU by a single masked grader, on a ordinal scale from 0 to 4 in 1/2 point increments. All scores were averaged and the mean of each animal used in student t-tests to compare severity of disease between experimental and wild type groups.
There were no significant differences between complement altered and wild type mice in any group (Table 1).
An absence of the anaphylatoxin receptors and thus lack of engagement by the anaphylatoxins C3a or C5a does not modify disease severity in EAU, nor does an absence of C5, the initial component of the membrane attack complex, despite previous evidence that a lack of C3 or inhibition of C3 activation results in significant disease amelioration. Possible explanations for these observations include engagement by the anaphylatoxins with receptors other than the C3aR or C5aR; formation of the MAC independent of C5; or that either of the anaphylatoxins, independently, is sufficient for proinflammatory effects in the eye.
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