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Nonetheless, over a decade after the identification of this important association, how innate immunity contributes to AMD remains unresolved. Pentraxin 3 (PTX3), an essential component of the innate immunity system that plays a non\u2010redundant role in controlling inflammation, regulates complement by interacting with complement components. Here, we show that PTX3 is induced by oxidative stress, a known cause of AMD, in the retinal pigmented epithelium (RPE). PTX3 deficiency <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> magnified complement activation induced by oxidative stress, leading to increased C3a, FB, and C3d, but not C5b\u20109 complex formation. Increased C3a levels, resulting from PTX3 deficiency, raised the levels of <jats:italic>Il1b<\/jats:italic> mRNA and secretion of activated interleukin (IL)\u20101\u03b2 by interacting with C3aR. Importantly, PTX3 deficiency augmented NLRP3 inflammasome activation, resulting in enhanced IL\u20101\u03b2, but not IL\u201018, production by the RPE. Thus, in the presence of PTX3 deficiency, the complement and inflammasome pathways worked in concert to produce IL\u20101\u03b2 in sufficient abundance to, importantly, result in macrophages accumulating in the choroid. These results demonstrate that PTX3 acts as an essential brake for complement and inflammasome activation by regulating the abundance of FH in the RPE, and provide critical insights into the complex interplay between oxidative stress and innate immunity in the early stages of AMD development. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4811","type":"journal-article","created":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T07:51:54Z","timestamp":1474617114000},"page":"495-506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Pentraxin 3 recruits complement factor H to protect against oxidative stress\u2010induced complement and inflammasome overactivation"],"prefix":"10.1002","volume":"240","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Cano","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins School of Medicine  Baltimore 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