Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin
Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging. Phospholipid m...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2001-10, Vol.104 (17), p.2107-2112 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | LINDNER, Jonathan R JI SONG CHRISTIANSEN, Jonathan KLIBANOV, Alexander L FANG XU LEY, Klaus |
| description | Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging.
Phospholipid microbubbles targeted to P-selectin (MB(p)) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB(p) and control microbubbles without antibody (MB) or with isotype control antibody (MB(iso)) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-alpha-stimulated wild-type mice. Retention of all microbubbles increased (P |
| doi_str_mv | 10.1161/hc4201.097061 |
| format | Article |
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Phospholipid microbubbles targeted to P-selectin (MB(p)) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB(p) and control microbubbles without antibody (MB) or with isotype control antibody (MB(iso)) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-alpha-stimulated wild-type mice. Retention of all microbubbles increased (P<0.05) with TNF-alpha treatment because of increased attachment to activated leukocytes. Extensive attachment of MB(p) directly to the venular endothelium or to adherent platelet-leukocyte aggregates was observed in TNF-alpha-stimulated mice, resulting in 4-fold greater (P<0.01) retention of MB(p) than either MB(iso) or MB. Enhanced retention of MB(p) was completely abolished in TNF-alpha-stimulated P-selectin-deficient mice. The ultrasound signal from microbubbles retained in inflamed tissue was assessed by contrast-enhanced renal ultrasound imaging of the kidneys of mice undergoing ischemia-reperfusion injury. In wild-type mice, this signal was significantly higher (P<0.05) for MB(p) (12+/-2 U) than either MB(iso) (6+/-3 U) or MB (5+/-3 U). In P-selectin-deficient mice, the signal for MB(p) was equivalent to that from control microbubbles.
Microvascular retention of microbubbles targeted to P-selectin produces strong signal enhancement on ultrasound imaging of inflamed tissue. These results suggest that site-targeted microbubbles may be used to assess inflammation, tissue injury, and other endothelial responses noninvasively with ultrasound.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/hc4201.097061</identifier><identifier>PMID: 11673354</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - metabolism ; Biological and medical sciences ; Cell Adhesion - drug effects ; Cell Adhesion - immunology ; Contrast Media - administration & dosage ; Contrast Media - chemistry ; Contrast Media - metabolism ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - immunology ; Endothelium, Vascular - physiopathology ; Inflammation - chemically induced ; Inflammation - diagnostic imaging ; Inflammation - physiopathology ; Injections, Intravenous ; Investigative techniques, diagnostic techniques (general aspects) ; Kidney - blood supply ; Kidney - diagnostic imaging ; Kidney - physiopathology ; Leukocytes - drug effects ; Leukocytes - immunology ; Leukocytes - metabolism ; Medical sciences ; Mice ; Mice, Knockout ; Micelles ; Muscle, Skeletal - blood supply ; Muscle, Skeletal - diagnostic imaging ; Muscle, Skeletal - drug effects ; P-Selectin - genetics ; P-Selectin - immunology ; P-Selectin - metabolism ; Phospholipids - chemistry ; Phospholipids - metabolism ; Predictive Value of Tests ; Reperfusion Injury - chemically induced ; Reperfusion Injury - diagnosis ; Reperfusion Injury - physiopathology ; Sensitivity and Specificity ; Tumor Necrosis Factor-alpha ; Ultrasonic investigative techniques ; Ultrasonography - methods ; Urinary system ; Venules - diagnostic imaging ; Venules - drug effects ; Venules - physiopathology</subject><ispartof>Circulation (New York, N.Y.), 2001-10, Vol.104 (17), p.2107-2112</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Oct 23, 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-86ad30ea861bf4c178fcdd742ba0ef6626b8854ec0c97d42557592a667aca71c3</citedby><cites>FETCH-LOGICAL-c428t-86ad30ea861bf4c178fcdd742ba0ef6626b8854ec0c97d42557592a667aca71c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14096424$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11673354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LINDNER, Jonathan R</creatorcontrib><creatorcontrib>JI SONG</creatorcontrib><creatorcontrib>CHRISTIANSEN, Jonathan</creatorcontrib><creatorcontrib>KLIBANOV, Alexander L</creatorcontrib><creatorcontrib>FANG XU</creatorcontrib><creatorcontrib>LEY, Klaus</creatorcontrib><title>Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging.
Phospholipid microbubbles targeted to P-selectin (MB(p)) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB(p) and control microbubbles without antibody (MB) or with isotype control antibody (MB(iso)) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-alpha-stimulated wild-type mice. Retention of all microbubbles increased (P<0.05) with TNF-alpha treatment because of increased attachment to activated leukocytes. Extensive attachment of MB(p) directly to the venular endothelium or to adherent platelet-leukocyte aggregates was observed in TNF-alpha-stimulated mice, resulting in 4-fold greater (P<0.01) retention of MB(p) than either MB(iso) or MB. Enhanced retention of MB(p) was completely abolished in TNF-alpha-stimulated P-selectin-deficient mice. The ultrasound signal from microbubbles retained in inflamed tissue was assessed by contrast-enhanced renal ultrasound imaging of the kidneys of mice undergoing ischemia-reperfusion injury. In wild-type mice, this signal was significantly higher (P<0.05) for MB(p) (12+/-2 U) than either MB(iso) (6+/-3 U) or MB (5+/-3 U). In P-selectin-deficient mice, the signal for MB(p) was equivalent to that from control microbubbles.
Microvascular retention of microbubbles targeted to P-selectin produces strong signal enhancement on ultrasound imaging of inflamed tissue. These results suggest that site-targeted microbubbles may be used to assess inflammation, tissue injury, and other endothelial responses noninvasively with ultrasound.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Adhesion - immunology</subject><subject>Contrast Media - administration & dosage</subject><subject>Contrast Media - chemistry</subject><subject>Contrast Media - metabolism</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - immunology</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - diagnostic imaging</subject><subject>Inflammation - physiopathology</subject><subject>Injections, Intravenous</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Kidney - blood supply</subject><subject>Kidney - diagnostic imaging</subject><subject>Kidney - physiopathology</subject><subject>Leukocytes - drug effects</subject><subject>Leukocytes - immunology</subject><subject>Leukocytes - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Micelles</subject><subject>Muscle, Skeletal - blood supply</subject><subject>Muscle, Skeletal - diagnostic imaging</subject><subject>Muscle, Skeletal - drug effects</subject><subject>P-Selectin - genetics</subject><subject>P-Selectin - immunology</subject><subject>P-Selectin - metabolism</subject><subject>Phospholipids - chemistry</subject><subject>Phospholipids - metabolism</subject><subject>Predictive Value of Tests</subject><subject>Reperfusion Injury - chemically induced</subject><subject>Reperfusion Injury - diagnosis</subject><subject>Reperfusion Injury - physiopathology</subject><subject>Sensitivity and Specificity</subject><subject>Tumor Necrosis Factor-alpha</subject><subject>Ultrasonic investigative techniques</subject><subject>Ultrasonography - methods</subject><subject>Urinary system</subject><subject>Venules - diagnostic imaging</subject><subject>Venules - drug effects</subject><subject>Venules - physiopathology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtLAzEQh4MotlaPXiUIHlfz2mT3KMUXFPRgz8tsNrFb9lEzWaT_vZEWPA3DfPNj5iPkmrN7zjV_2FglGL9npWGan5A5z4XKVC7LUzJnjJWZkULMyAXiNrVamvyczNKmkTJXc-LXXQyA4zQ0FBAdYu-GSEdP28F30PcQ23GgkMbBDdDR2CJOLk23U9jTnzZuaN_aMNZTXXcOaYTw5aJraBzpR4aucza2wyU589ChuzrWBVk_P30uX7PV-8vb8nGVpS-KmBUaGskcFJrXXlluCm-bxihRA3Nea6HrosiVs8yWplEiz01eCtDagAXDrVyQ20PuLozfk8NYbccppLuxElwkFVKWCcoOUDobMThf7ULbQ9hXnFV_UquD1OogNfE3x9Cp7l3zTx8tJuDuCABa6HyAwbb4zylWaiWU_AVPV4BM</recordid><startdate>20011023</startdate><enddate>20011023</enddate><creator>LINDNER, Jonathan R</creator><creator>JI SONG</creator><creator>CHRISTIANSEN, Jonathan</creator><creator>KLIBANOV, Alexander L</creator><creator>FANG XU</creator><creator>LEY, Klaus</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope></search><sort><creationdate>20011023</creationdate><title>Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin</title><author>LINDNER, Jonathan R ; JI SONG ; CHRISTIANSEN, Jonathan ; KLIBANOV, Alexander L ; FANG XU ; LEY, Klaus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-86ad30ea861bf4c178fcdd742ba0ef6626b8854ec0c97d42557592a667aca71c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antibodies, Monoclonal - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Adhesion - immunology</topic><topic>Contrast Media - administration & dosage</topic><topic>Contrast Media - chemistry</topic><topic>Contrast Media - metabolism</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - immunology</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - diagnostic imaging</topic><topic>Inflammation - physiopathology</topic><topic>Injections, Intravenous</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Kidney - blood supply</topic><topic>Kidney - diagnostic imaging</topic><topic>Kidney - physiopathology</topic><topic>Leukocytes - drug effects</topic><topic>Leukocytes - immunology</topic><topic>Leukocytes - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Micelles</topic><topic>Muscle, Skeletal - blood supply</topic><topic>Muscle, Skeletal - diagnostic imaging</topic><topic>Muscle, Skeletal - drug effects</topic><topic>P-Selectin - genetics</topic><topic>P-Selectin - immunology</topic><topic>P-Selectin - metabolism</topic><topic>Phospholipids - chemistry</topic><topic>Phospholipids - metabolism</topic><topic>Predictive Value of Tests</topic><topic>Reperfusion Injury - chemically induced</topic><topic>Reperfusion Injury - diagnosis</topic><topic>Reperfusion Injury - physiopathology</topic><topic>Sensitivity and Specificity</topic><topic>Tumor Necrosis Factor-alpha</topic><topic>Ultrasonic investigative techniques</topic><topic>Ultrasonography - methods</topic><topic>Urinary system</topic><topic>Venules - diagnostic imaging</topic><topic>Venules - drug effects</topic><topic>Venules - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LINDNER, Jonathan R</creatorcontrib><creatorcontrib>JI SONG</creatorcontrib><creatorcontrib>CHRISTIANSEN, Jonathan</creatorcontrib><creatorcontrib>KLIBANOV, Alexander L</creatorcontrib><creatorcontrib>FANG XU</creatorcontrib><creatorcontrib>LEY, Klaus</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LINDNER, Jonathan R</au><au>JI SONG</au><au>CHRISTIANSEN, Jonathan</au><au>KLIBANOV, Alexander L</au><au>FANG XU</au><au>LEY, Klaus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2001-10-23</date><risdate>2001</risdate><volume>104</volume><issue>17</issue><spage>2107</spage><epage>2112</epage><pages>2107-2112</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging.
Phospholipid microbubbles targeted to P-selectin (MB(p)) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB(p) and control microbubbles without antibody (MB) or with isotype control antibody (MB(iso)) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-alpha-stimulated wild-type mice. Retention of all microbubbles increased (P<0.05) with TNF-alpha treatment because of increased attachment to activated leukocytes. Extensive attachment of MB(p) directly to the venular endothelium or to adherent platelet-leukocyte aggregates was observed in TNF-alpha-stimulated mice, resulting in 4-fold greater (P<0.01) retention of MB(p) than either MB(iso) or MB. Enhanced retention of MB(p) was completely abolished in TNF-alpha-stimulated P-selectin-deficient mice. The ultrasound signal from microbubbles retained in inflamed tissue was assessed by contrast-enhanced renal ultrasound imaging of the kidneys of mice undergoing ischemia-reperfusion injury. In wild-type mice, this signal was significantly higher (P<0.05) for MB(p) (12+/-2 U) than either MB(iso) (6+/-3 U) or MB (5+/-3 U). In P-selectin-deficient mice, the signal for MB(p) was equivalent to that from control microbubbles.
Microvascular retention of microbubbles targeted to P-selectin produces strong signal enhancement on ultrasound imaging of inflamed tissue. These results suggest that site-targeted microbubbles may be used to assess inflammation, tissue injury, and other endothelial responses noninvasively with ultrasound.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>11673354</pmid><doi>10.1161/hc4201.097061</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - metabolism Biological and medical sciences Cell Adhesion - drug effects Cell Adhesion - immunology Contrast Media - administration & dosage Contrast Media - chemistry Contrast Media - metabolism Endothelium, Vascular - drug effects Endothelium, Vascular - immunology Endothelium, Vascular - physiopathology Inflammation - chemically induced Inflammation - diagnostic imaging Inflammation - physiopathology Injections, Intravenous Investigative techniques, diagnostic techniques (general aspects) Kidney - blood supply Kidney - diagnostic imaging Kidney - physiopathology Leukocytes - drug effects Leukocytes - immunology Leukocytes - metabolism Medical sciences Mice Mice, Knockout Micelles Muscle, Skeletal - blood supply Muscle, Skeletal - diagnostic imaging Muscle, Skeletal - drug effects P-Selectin - genetics P-Selectin - immunology P-Selectin - metabolism Phospholipids - chemistry Phospholipids - metabolism Predictive Value of Tests Reperfusion Injury - chemically induced Reperfusion Injury - diagnosis Reperfusion Injury - physiopathology Sensitivity and Specificity Tumor Necrosis Factor-alpha Ultrasonic investigative techniques Ultrasonography - methods Urinary system Venules - diagnostic imaging Venules - drug effects Venules - physiopathology |
| title | Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin |
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