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CD40L-positive platelets induce CD40L expression de novo in endothelial cells: adding a loop to microvascular inflammation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Danese, Silvio Scaldaferri, Franco Papa, Alfredo Pola, Roberto Gasbarrini, Antonio Sgambato, Allesandro Cittadini, Achille |
| Copyright Year | 2004 |
| Abstract | Expression De Novo in Endothelial Cells: Adding a Loop to Microvascular Inflammation To the Editor: We read with great interest the article by Wagner et al, in which the authors elegantly showed that membrane bound CD154 (CD40 ligand [L]) expressed by T-cells can effectively trigger CD40L expression by endothelial cells. More importantly, the authors demonstrated a functional activity of endothelium-associated CD40L, thus revealing a novel costimulatory activity in monocyte–endothelial interactions.1 We have recently performed a series of experiments that aimed to study CD40L induction by endothelial cells, in particular assessing the consequences of the interactions between CD40L positive platelets with CD40 bearing endothelial cells. CD40L expression was evaluated by flow cytometry in human intestinal microvascular endothelial cells (HIMEC) cultured alone, with resting and thrombin activated platelets, or stimulated with different activators, including interleukin (IL)-1 , tumor necrosis factor (TNF), and interferon (INF). Functional CD40–CD40L interactions were interrupted by using anti-CD40L specific antibodies, as reported.2 We found that CD40L was virtually absent in resting HIMEC (Figure A), and that all the potent proinflammatory molecules, such as IL-1 , TNF, and INF, failed to induce CD40L expression, even though they were able to trigger HIMEC activation by upregulation of adhesion molecules (not shown). Resting platelets only slightly induced membrane bound endothelial CD40L (Figure B); in contrast, when endothelial cells were cultured with thrombin-positive CD40L platelets, HIMEC strongly upregulated CD40L expression (Figure C). Specificity of the CD40/CD40L pathway activation was demonstrated by platelet-CD40L blockade, as addressed by the strong inhibition induced by the use of the anti-CD40L antibodies (Figure D). Taken together, our results extend the findings by Wagner et al, suggesting that platelets are a novel cell type that could be implicated in mediating CD40L-endothelial expression, thus strengthening the concept that activated platelets trigger endothelial CD40-dependent inflammation.3 At sites of intense endothelial activation and inflammation, such as during atherosclerosis or chronic intestinal inflammation in inflammatory bowel disease, where platelets express CD40L and are at direct contact with CD40 bearing endothelium,4 CD40L upregulation by endothelial cells could be a novel element in immune response amplification and in mediating crosstalk and activation signals toward CD40 positive cells, such as monocytes, B-cells, T-cells, and platelets. An extremely high number ( 10) of platelets circulate in the peripheral blood, and their number and activation state is increased in several inflammatory conditions. Thus, because they express and are the major source of CD40L in the blood, CD40L-platelet–dependent CD40L-endothelial upregulation might represent a new pathway in the amplification of endothelium-dependent inflammation. Furthermore, targeting these interactions could be considered a potential therapeutic approach to blocking vascular inflammation not only in atherosclerosis, but also in chronically inflamed tissues, where the endothelium regulates leukocyte traffic and influx into the interstitium. |
| Starting Page | e162 |
| Ending Page | e162 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/24/9/e162.full.pdf |
| PubMed reference number | 15345520v1 |
| Volume Number | 24 |
| Issue Number | 9 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Atherosclerosis Blood Platelets Body tissue CD40 Ligand Cerebrovascular Disorders Cross Reactions Endothelial Cells Flow Cytometry Inflammation Inflammatory Bowel Diseases Interleukins Intestinal Diseases Intestines Leukocytes Ligands Platelet Count measurement Rest Tissue membrane Tumor Necrosis Factors Up-Regulation (Physiology) cellular targeting peripheral blood |
| Content Type | Text |
| Resource Type | Article |
