Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo
The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain...
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| Veröffentlicht in: | The Journal of experimental medicine 2006-05, Vol.203 (5), p.1221-1233 |
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| creator | Massberg, Steffen Konrad, Ildiko Schürzinger, Katrin Lorenz, Michael Schneider, Simon Zohlnhoefer, Dietlind Hoppe, Katharina Schiemann, Matthias Kennerknecht, Elisabeth Sauer, Susanne Schulz, Christian Kerstan, Sandra Rudelius, Martina Seidl, Stefan Sorge, Falko Langer, Harald Peluso, Mario Goyal, Pankaj Vestweber, Dietmar Emambokus, Nikla R Busch, Dirk H Frampton, Jon Gawaz, Meinrad |
| description | The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury. |
| format | Article |
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Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. 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Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.</description><subject>Animals</subject><subject>Antigens, Differentiation - metabolism</subject><subject>Arteries - injuries</subject><subject>Arteries - metabolism</subject><subject>Arteries - pathology</subject><subject>Blood Platelets - pathology</subject><subject>Blood Platelets - secretion</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Bone Marrow Cells - pathology</subject><subject>Cell Adhesion</subject><subject>Cell Movement</subject><subject>Chemokine CXCL12</subject><subject>Chemokines, CXC - secretion</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - pathology</subject><subject>Mice</subject><subject>Microscopy, Fluorescence</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Myocytes, Smooth Muscle - pathology</subject><subject>Platelet Activation</subject><subject>Recovery of Function</subject><subject>Stem Cells - metabolism</subject><subject>Stem Cells - pathology</subject><subject>Thrombosis - metabolism</subject><subject>Thrombosis - pathology</subject><issn>0022-1007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kD1PwzAQhj2AaCn8BeSJLZK_4iQjqviSKsHQPbLjCzVy4mA7QYz8c1xRmG6453303p2hNSGMFZSQaoUuY3wnhApRygu0olLSumrEGn2_OpXAQYo4QhcgAY4p-EE53IFzhYFgFzC4V13yAVPlpoPCajQ4ZHy2CWs_Ah5UCP7zn56Cf4PRHhNHS8TJYxVS3mZvOmS_ttiOeLGLv0LnvXIRrk9zg_YP9_vtU7F7eXze3u2KqRSiaCTQSmtakp5pwg1jPVecMa5qrahuJGekAyilJEbUnHaSc10J3clamMr0fINuf7W528cMMbWDjcdyagQ_x1ZWTU0YJRm8OYGzHsC0U7D5uq_272f8Bz_waZ4</recordid><startdate>20060515</startdate><enddate>20060515</enddate><creator>Massberg, Steffen</creator><creator>Konrad, Ildiko</creator><creator>Schürzinger, Katrin</creator><creator>Lorenz, Michael</creator><creator>Schneider, Simon</creator><creator>Zohlnhoefer, Dietlind</creator><creator>Hoppe, Katharina</creator><creator>Schiemann, Matthias</creator><creator>Kennerknecht, Elisabeth</creator><creator>Sauer, Susanne</creator><creator>Schulz, Christian</creator><creator>Kerstan, Sandra</creator><creator>Rudelius, Martina</creator><creator>Seidl, Stefan</creator><creator>Sorge, Falko</creator><creator>Langer, Harald</creator><creator>Peluso, Mario</creator><creator>Goyal, Pankaj</creator><creator>Vestweber, Dietmar</creator><creator>Emambokus, Nikla R</creator><creator>Busch, Dirk H</creator><creator>Frampton, Jon</creator><creator>Gawaz, Meinrad</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20060515</creationdate><title>Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo</title><author>Massberg, Steffen ; 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Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.</abstract><cop>United States</cop><pmid>16618794</pmid><tpages>13</tpages></addata></record> |
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| subjects | Animals Antigens, Differentiation - metabolism Arteries - injuries Arteries - metabolism Arteries - pathology Blood Platelets - pathology Blood Platelets - secretion Bone Marrow Cells - metabolism Bone Marrow Cells - pathology Cell Adhesion Cell Movement Chemokine CXCL12 Chemokines, CXC - secretion Endothelium, Vascular - metabolism Endothelium, Vascular - pathology Mice Microscopy, Fluorescence Myocytes, Smooth Muscle - metabolism Myocytes, Smooth Muscle - pathology Platelet Activation Recovery of Function Stem Cells - metabolism Stem Cells - pathology Thrombosis - metabolism Thrombosis - pathology |
| title | Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo |
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