Mesenteric microvascular inflammatory responses to systemic hypoxia are mediated by PAF and LTB4

Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, Kansas 66160 Systemic hypoxia produces a rapid microvascular inflammatory response characterized by increased reactive oxygen species (ROS) levels, leukocyte-endothelial adherence and emigration...

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Veröffentlicht in:Journal of applied physiology (1985) 2003-06, Vol.94 (6), p.2313-2322
Hauptverfasser: Casillan, Alfred J, Gonzalez, Norberto C, Johnson, Jennifer S, Steiner, Dawn R. S, Wood, John G
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container_end_page 2322
container_issue 6
container_start_page 2313
container_title Journal of applied physiology (1985)
container_volume 94
creator Casillan, Alfred J
Gonzalez, Norberto C
Johnson, Jennifer S
Steiner, Dawn R. S
Wood, John G
description Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, Kansas 66160 Systemic hypoxia produces a rapid microvascular inflammatory response characterized by increased reactive oxygen species (ROS) levels, leukocyte-endothelial adherence and emigration, and increased vascular permeability. The lipid inflammatory mediator leukotriene B 4 (LTB 4 ) is involved in the early hypoxia-induced responses (ROS generation and leukocyte adherence). Whether other lipid inflammatory mediators participate in this phenomenon is not known. The objective of these experiments was to study the role of platelet-activating factor (PAF) in the microvascular inflammatory response to hypoxia and its potential interactions with LTB 4 in this response. Intravital microscopy was used to examine mesenteric venules of anesthetized rats. We found that WEB-2086, a PAF receptor antagonist, completely prevented the increase in ROS levels and leukocyte adherence during a brief reduction in inspired P O 2 to anesthetized rats; administration of either WEB-2086 or the LTB 4 antagonist LTB 4 -DMA attenuated leukocyte emigration and the increase in vascular permeability to the same extent during prolonged systemic hypoxia in conscious rats. Furthermore, no additive effect was observed in either response when both antagonists were administered simultaneously. This study demonstrates a role for PAF in the rapid microvascular inflammatory response to hypoxia, as well as contributions of PAF and LTB 4 to the slowly developing responses observed during sustained hypoxia. The incomplete blockade of the hypoxia-induced increases in vascular permeability and leukocyte emigration by combined administration of both antagonists indicates that factors in addition to LTB 4 and PAF participate in these phenomena. leukocyte-endothelial adhesive interactions; leukocyte emigration; microcirculation; intravital microscopy; inflammatory mediators
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S ; Wood, John G</creator><creatorcontrib>Casillan, Alfred J ; Gonzalez, Norberto C ; Johnson, Jennifer S ; Steiner, Dawn R. S ; Wood, John G</creatorcontrib><description>Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, Kansas 66160 Systemic hypoxia produces a rapid microvascular inflammatory response characterized by increased reactive oxygen species (ROS) levels, leukocyte-endothelial adherence and emigration, and increased vascular permeability. The lipid inflammatory mediator leukotriene B 4 (LTB 4 ) is involved in the early hypoxia-induced responses (ROS generation and leukocyte adherence). Whether other lipid inflammatory mediators participate in this phenomenon is not known. The objective of these experiments was to study the role of platelet-activating factor (PAF) in the microvascular inflammatory response to hypoxia and its potential interactions with LTB 4 in this response. Intravital microscopy was used to examine mesenteric venules of anesthetized rats. We found that WEB-2086, a PAF receptor antagonist, completely prevented the increase in ROS levels and leukocyte adherence during a brief reduction in inspired P O 2 to anesthetized rats; administration of either WEB-2086 or the LTB 4 antagonist LTB 4 -DMA attenuated leukocyte emigration and the increase in vascular permeability to the same extent during prolonged systemic hypoxia in conscious rats. Furthermore, no additive effect was observed in either response when both antagonists were administered simultaneously. This study demonstrates a role for PAF in the rapid microvascular inflammatory response to hypoxia, as well as contributions of PAF and LTB 4 to the slowly developing responses observed during sustained hypoxia. The incomplete blockade of the hypoxia-induced increases in vascular permeability and leukocyte emigration by combined administration of both antagonists indicates that factors in addition to LTB 4 and PAF participate in these phenomena. leukocyte-endothelial adhesive interactions; leukocyte emigration; microcirculation; intravital microscopy; inflammatory mediators</description><identifier>ISSN: 8750-7587</identifier><identifier>EISSN: 1522-1601</identifier><identifier>DOI: 10.1152/japplphysiol.00047.2002</identifier><identifier>PMID: 12598480</identifier><identifier>CODEN: JAPHEV</identifier><language>eng</language><publisher>Bethesda, MD: Am Physiological Soc</publisher><subject>Animals ; Azepines - pharmacology ; Biological and medical sciences ; Capillary Permeability - drug effects ; Cell Adhesion - drug effects ; Fluorescence ; Fundamental and applied biological sciences. 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S</creatorcontrib><creatorcontrib>Wood, John G</creatorcontrib><title>Mesenteric microvascular inflammatory responses to systemic hypoxia are mediated by PAF and LTB4</title><title>Journal of applied physiology (1985)</title><addtitle>J Appl Physiol (1985)</addtitle><description>Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, Kansas 66160 Systemic hypoxia produces a rapid microvascular inflammatory response characterized by increased reactive oxygen species (ROS) levels, leukocyte-endothelial adherence and emigration, and increased vascular permeability. The lipid inflammatory mediator leukotriene B 4 (LTB 4 ) is involved in the early hypoxia-induced responses (ROS generation and leukocyte adherence). Whether other lipid inflammatory mediators participate in this phenomenon is not known. The objective of these experiments was to study the role of platelet-activating factor (PAF) in the microvascular inflammatory response to hypoxia and its potential interactions with LTB 4 in this response. Intravital microscopy was used to examine mesenteric venules of anesthetized rats. We found that WEB-2086, a PAF receptor antagonist, completely prevented the increase in ROS levels and leukocyte adherence during a brief reduction in inspired P O 2 to anesthetized rats; administration of either WEB-2086 or the LTB 4 antagonist LTB 4 -DMA attenuated leukocyte emigration and the increase in vascular permeability to the same extent during prolonged systemic hypoxia in conscious rats. Furthermore, no additive effect was observed in either response when both antagonists were administered simultaneously. This study demonstrates a role for PAF in the rapid microvascular inflammatory response to hypoxia, as well as contributions of PAF and LTB 4 to the slowly developing responses observed during sustained hypoxia. The incomplete blockade of the hypoxia-induced increases in vascular permeability and leukocyte emigration by combined administration of both antagonists indicates that factors in addition to LTB 4 and PAF participate in these phenomena. leukocyte-endothelial adhesive interactions; leukocyte emigration; microcirculation; intravital microscopy; inflammatory mediators</description><subject>Animals</subject><subject>Azepines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Capillary Permeability - drug effects</subject><subject>Cell Adhesion - drug effects</subject><subject>Fluorescence</subject><subject>Fundamental and applied biological sciences. 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Psychology</topic><topic>Hypoxia - complications</topic><topic>Hypoxia - physiopathology</topic><topic>Inflammation</topic><topic>Leukocytes</topic><topic>Leukocytes - physiology</topic><topic>Leukotriene B4 - analogs &amp; derivatives</topic><topic>Leukotriene B4 - metabolism</topic><topic>Leukotriene B4 - pharmacology</topic><topic>Male</topic><topic>Microcirculation - drug effects</topic><topic>Microscopy</topic><topic>Molecular and cellular biology</topic><topic>Oxidants - pharmacology</topic><topic>Oxygen</topic><topic>Platelet Activating Factor - metabolism</topic><topic>Platelet Activating Factor - pharmacology</topic><topic>Platelet Membrane Glycoproteins - antagonists &amp; inhibitors</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Receptors, Cell Surface - antagonists &amp; inhibitors</topic><topic>Receptors, G-Protein-Coupled</topic><topic>Receptors, Leukotriene B4 - antagonists &amp; inhibitors</topic><topic>Rhodamines</topic><topic>Splanchnic Circulation - drug effects</topic><topic>Triazoles - pharmacology</topic><topic>Vasculitis - etiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Casillan, Alfred J</creatorcontrib><creatorcontrib>Gonzalez, Norberto C</creatorcontrib><creatorcontrib>Johnson, Jennifer S</creatorcontrib><creatorcontrib>Steiner, Dawn R. 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S</au><au>Wood, John G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesenteric microvascular inflammatory responses to systemic hypoxia are mediated by PAF and LTB4</atitle><jtitle>Journal of applied physiology (1985)</jtitle><addtitle>J Appl Physiol (1985)</addtitle><date>2003-06-01</date><risdate>2003</risdate><volume>94</volume><issue>6</issue><spage>2313</spage><epage>2322</epage><pages>2313-2322</pages><issn>8750-7587</issn><eissn>1522-1601</eissn><coden>JAPHEV</coden><abstract>Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, Kansas 66160 Systemic hypoxia produces a rapid microvascular inflammatory response characterized by increased reactive oxygen species (ROS) levels, leukocyte-endothelial adherence and emigration, and increased vascular permeability. The lipid inflammatory mediator leukotriene B 4 (LTB 4 ) is involved in the early hypoxia-induced responses (ROS generation and leukocyte adherence). Whether other lipid inflammatory mediators participate in this phenomenon is not known. The objective of these experiments was to study the role of platelet-activating factor (PAF) in the microvascular inflammatory response to hypoxia and its potential interactions with LTB 4 in this response. Intravital microscopy was used to examine mesenteric venules of anesthetized rats. We found that WEB-2086, a PAF receptor antagonist, completely prevented the increase in ROS levels and leukocyte adherence during a brief reduction in inspired P O 2 to anesthetized rats; administration of either WEB-2086 or the LTB 4 antagonist LTB 4 -DMA attenuated leukocyte emigration and the increase in vascular permeability to the same extent during prolonged systemic hypoxia in conscious rats. Furthermore, no additive effect was observed in either response when both antagonists were administered simultaneously. This study demonstrates a role for PAF in the rapid microvascular inflammatory response to hypoxia, as well as contributions of PAF and LTB 4 to the slowly developing responses observed during sustained hypoxia. The incomplete blockade of the hypoxia-induced increases in vascular permeability and leukocyte emigration by combined administration of both antagonists indicates that factors in addition to LTB 4 and PAF participate in these phenomena. leukocyte-endothelial adhesive interactions; leukocyte emigration; microcirculation; intravital microscopy; inflammatory mediators</abstract><cop>Bethesda, MD</cop><pub>Am Physiological Soc</pub><pmid>12598480</pmid><doi>10.1152/japplphysiol.00047.2002</doi><tpages>10</tpages></addata></record>
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subjects Animals
Azepines - pharmacology
Biological and medical sciences
Capillary Permeability - drug effects
Cell Adhesion - drug effects
Fluorescence
Fundamental and applied biological sciences. Psychology
Hypoxia - complications
Hypoxia - physiopathology
Inflammation
Leukocytes
Leukocytes - physiology
Leukotriene B4 - analogs & derivatives
Leukotriene B4 - metabolism
Leukotriene B4 - pharmacology
Male
Microcirculation - drug effects
Microscopy
Molecular and cellular biology
Oxidants - pharmacology
Oxygen
Platelet Activating Factor - metabolism
Platelet Activating Factor - pharmacology
Platelet Membrane Glycoproteins - antagonists & inhibitors
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species - metabolism
Receptors, Cell Surface - antagonists & inhibitors
Receptors, G-Protein-Coupled
Receptors, Leukotriene B4 - antagonists & inhibitors
Rhodamines
Splanchnic Circulation - drug effects
Triazoles - pharmacology
Vasculitis - etiology
title Mesenteric microvascular inflammatory responses to systemic hypoxia are mediated by PAF and LTB4
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