Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34660
Rettig, L; Haen, S P; Bittermann, A G; von Boehmer, L; Curioni, A; Krämer, S D; Knuth, A; Pascolo, S (2010). Particle size and activation threshold: a new dimension of danger signaling. Blood, 115(22):4533-4541.
Previous studies have shown that single-stranded RNA (ssRNA) mixed with protamine forms particles and activates immune cells through Toll-like receptors (TLRs). We have found that the size of protamine-RNA particles generated depends on the electrolyte content when mixing the 2 components. Moreover, we have evidenced that (1) nanometric particles induce production of interferon-alpha, whereas (2) micrometric particles mainly induce production of tumor necrosis factor-alpha (TNF-alpha) in human immune cells. We found that the mechanisms underlying these observations are (1) nanoparticles but not microparticles are selectively phagocytosed by plasmacytoid dendritic cells (pDCs), which produce interferon-alpha and (2) monocytes that produce TNF-alpha have a higher activation threshold than that of pDCs. Thus, at the same time as sensing pathogen-associated molecular patterns such as ssRNA, the immune system distinguishes the size of the associated structure in such a way as to trigger the adapted antivirus (nanometric) or antibacterial/antifungal (micrometric) immune response. Our results introduce a new dimension in danger signaling--how size qualitatively affects innate response.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Microscopy and Image Analysis |
04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Date:||03 June 2010|
|Deposited On:||07 Jul 2010 00:37|
|Last Modified:||23 Nov 2012 16:23|
|Publisher:||American Society of Hematology|
|Additional Information:||This research was originally published in Blood. 2010, 115(22):4533-4541. Copyright by the American Society of Hematology|
|Publisher DOI:||10.1182/blood-2009- 11-247817|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page