The intriguing normal acute inflammatory response in mice lacking vimentin

Abstract

SummaryNeutrophils express only two intermediate filament proteins, vimentin and, to a lesser extent, lamin B. Lamin B mutant mice die shortly after birth; however, mice lacking vimentin (vim -/-) develop and reproduce normally. Herein, we investigate for the first time the role of vimentin in general inflammation in vivo and in neutrophil functions ex vivo. Using the murine air pouch model, we show that the inflammatory response induced by lipopolysaccharide, interleukin-21 or carageenan is, intriguingly, uncompromised in vim -/-mice and that neutrophil functions are not altered ex vivo. Our results suggest that vimentin is dispensable for the establishment of an acute inflammatory response in vivo. In addition, based on several criteria presented in this study, one has to accept the existence of a very complex compensatory mechanism to explain the intriguing normal inflammatory response in absence of vimentin.

Leukocyte transmigration is modulated by chemokine‐mediated PI3Kγ‐dependent phosphorylation of vimentin

“…In potential contrast with our findings, a recent report indicates that the lack of vimentin does not impair leukocyte recruitment in response to LPS, IL-21 or carrageenan [42]. However, the same study proposes that compensatory mechanisms might explain this lack of phenotype.…”

“…Unexpectedly, PI3Kg-null BMDM showed decreased transmigration not only at early but also at later time points, when vimentin phosphorylation did not depend on PI3Kg signaling. However, a possible explanation is that alteration of early phosphorylation events is sufficient to cause a delayed onset of transmigration that cannot be regained with time.In potential contrast with our findings, a recent report indicates that the lack of vimentin does not impair leukocyte recruitment in response to LPS, IL-21 or carrageenan [42]. However, the same study proposes that compensatory mechanisms might explain this lack of phenotype.…”

Vimentin Filaments Support Extension of Tubulin-Based Microtentacles in Detached Breast Tumor Cells

“…Interestingly, blotting with a pan-intermediate filament antibody indicated that as vimentin levels decreased, a new intermediate filament protein of ~65kDa increased, suggesting a compensatory response to siRNA-mediated vimentin reduction. Such a compensatory mechanism has been proposed for why vimentin knockout mice are viable and phenotypically normal (28), and illustrates the potential limitations of siRNA-mediated downregulation of such an abundant gene with numerous redundant family members. Nevertheless, expression of GFP-Vim-DN disrupted endogenous vimentin filaments within one day and provides genetic evidence that vimentin directly supports the molecular mechanism underlying microtentacles in detached breast tumor cells.…”

Titanium dioxide (TiO2) nanoparticles induce neutrophil influx and local production of several pro-inflammatory mediators in vivo

“…After 9 h, the number of attracted leukocytes started to decline, but the total number of cells was still significantly greater than in controls, and then declined to levels similar to controls over time. In contrast to TiO 2 , CRGN, known to induce leukocyte influx for a longer period of time [19,20], significantly increased the number of cells after 9 h, which increased after 12 h and 24 h. Fig. 2B (upper panel) illustrates that PMNs are the main cell type attracted by TiO 2 NPs as identified by cytology.…”