Cell biology of trauma PDF
Preview Cell biology of trauma
Cell Biology of Trauma Editedby John J. Lemasters, M.D., Ph.D. Professor of Cell Biology and Anatomy University of North Carolina at Chapel Hill Constance Oliver, Ph.D. Biomedical Science and Technology Office of Naval Research Arlington, Virginia CRC Press BocaRaton London Tokyo LibraryofCongress Cataloging-in-Publication Data Cellbiology oftrauma/editedbyJohnJ. Lemasters andConstance Oliver. p. cm. Includesbibliographicalreferences andindex. ISBN0-8493-2453-X 1. Traumatic shock. 2. Pathology, Molecular. I. Lemasters,John J. II. Oliver, Constance. RB150.S5C45 1995 617.2' l-dc20 94-30688 CIP This book contains information obtained from authentic and highly regarded sources. Re printed materialisquotedwith permission,andsourcesare indicated.Awidevarietyofreferences are listed. Reasonable efforts have been made to publish reliable data and information, but the authorandthepublishercannotassumeresponsibility forthe validity ofall materials orforthe consequences oftheiruse. Neither thisbooknoranypartmaybereproduced or transmittedin anyformor byanymeans, electronic ormechanical,includingphotocopying,microfilming, andrecording,orbyanyinfor mation storage orretrieval system,withoutpriorpermissioninwritingfromthepublisher. All rights reserved. Authorization to photocopy items for internal or personal use, or the personalorinternaluseof specificclients,maybegrantedbyCRCPress,Inc., providedthat$.50 perpagephotocopiedispaiddirectlyto CopyrightClearanceCenter,27 CongressStreet, Salem, MA01970USA. Thefeecodeforusersof theTransactionalReportingServiceis ISBN0-8493- 2453-X/95/$0.00+$.50.The fee issubjecttochangewithoutnotice. Fororganizationsthathave beengrantedaphotocopylicenseby the CCC, a separate systemofpaymenthas beenarranged. CRCPress,Inc.’s consentdoesnotextendtocopyingforgeneraldistribution,forpromotion, forcreatingnewworks, orforresale.Specificpermissionmustbeobtainedin writingfromCRC Press forsuchcopying. Direct all inquiries to CRC Press, Inc., 2000 Corporate Blvd., N.W., Boca Raton, Florida 33431. © 1995by CRCPress,Inc. Noclaim tooriginalU.S. Governmentworks International StandardBookNumber0-8493-2453-X Library ofCongress CardNumber94-30688 Printedinthe UnitedStates ofAmerica 1 2 3 4 5 6 7 8 9 0 Printedon acid-freepaper PREFACE The response of a multicellularorganism to traumaisremarkably complex — virtually all the systems ofthe bodyrespondto anassaultagainstits physical integrity. Traditionaltraumaresearchhas attemptedto bothcharacterizethose systemic responses and identify the pathologic mediators invoked, and to developpharmacologicinterventionsthatsuppress unfavorable responses and/or promote favorable ones. The research reported in this volume represents an other approach to trauma biology: a look at trauma’s consequences at the molecular level in order to intervene at the cellular level. This approach has been made possible by the recent explosion ofourknowledge regarding how cells respond to their environment from the membrane to the gene, and the evolution of elegant new tools to examine cellularresponses atthe molecular level.Realizationofthe potentialofcell biologyfordirectingtraumaresearch ers to new therapeutic targets formed the basis for a program initiated by the OfficeofNavalResearchin 1988entitled“Cell BiologyofTrauma.”Many of the investigations described in this book began under that program, and they formedthe nucleus for a workshop ofthe same nameatthe University ofNorth Carolinaat ChapelHill onJune 18-20,1993, organizedby Dr. JohnJ. Lemasters ofthe University and Dr. Constance Oliver of the Office ofNaval Research. This volume is an outgrowth of that workshop. A recurrent theme in trauma, ranging from cold injury to hemorrhage, is ischemia resulting from impaired blood flow. Obviously, the organs most affected by ischemia are those that demand the most oxygen and substrate to function. These organsare the heart, brain,andkidneyandtheyare particularly vulnerableto impairment ofvascularflow. Manyofthelethalconsequencesof trauma, especially in hemorrhage, can be traced to organ failure secondary to ischemic injury. Ischemic injury at the cellular level can be considered to consist of three phases: (1) the assault on the cell caused by the initial sudden deprivation of oxygen and nutrients, (2) the cellular adaptation to hypoxia in the absence of exogenous nutrientsor removal ofwaste products,and(3)the cellularresponse to the reintroduction ofoxygen and exogenous nutrients (reperfusion). While considerable research has addressed the consequences of reperfusion, with a focus on the toxic consequences ofexcess calcium ion uptake and membrane damageby freeradicals, little attention hasbeenpaid to the molecularevents, particularly the adaptive events, occurring in the first two phases. Those molecular events, together with the development of therapeutic agents that corrector exploit thoseevents,comprisethe focusofthisbook. Cytoprotective agents discussed here consist of drugs of the 21-amino steroid family, the prostaglandin polymer Calciphor, glycine, and modified perfusion/resuscita tionfluids capable ofpreventingcytotoxicpHchanges. Thelatterwork points to a need to critically reassess the role ofcellular acidosis and the therapeutic procedures used to compensate for it in emergency medicine. As ourawareness ofmechanisms forcellularregulationexpands, sodo the potentialtherapeutictargetsin trauma. Itshouldalways be remembered that an organ fails because its cells fail. Sorting out the intrinsic cellular processes leadingto cell death from thoseimposed by systemicmediatorsand inflamma tion will not be simple, but treatments that focus on the cell’s symptoms and responses are likely to be broadly applicable in trauma medicine. Jeannine A. Majde, Ph.D. Program Manager, Biomedical Science and Technology Office of Naval Research THE EDITORS JohnJ. Lemasters,M.D., Ph.D.,isProfessorofCellBiology andAnatomy and Member of the Curriculum in Toxicology at the University of North Carolina at Chapel Hill. Dr. Lemasters graduated in 1969 from Yale Univer sity, New Haven, Connecticut, with a B.A. degree in psychology (cum laude with honors) and obtained his M.D. degree and Ph.D. degree in anatomy and cell biology in 1975 from the Johns Hopkins University School ofMedicine, Baltimore, Maryland. Dr. Lemasters is a member of the American Association for the Advance ment ofScience, the American Association fortheStudy ofLiverDiseases, the AmericanAssociationofAnatomists,the AmericanHeartAssociation, Coun cil on Circulation, the American Physiological Society, the American Society forBiochemistry andMolecularBiology, the Biophysical Society, the Ameri can Society for Cell Biology, the Microscopy Society of America, and the Society of Toxicology. Dr. Lemasters serves on the editorial boards of the American Journal of Physiology: CellPhysiology, Cell Calcium, and Hepatology. He has been the recipient of many research grants from the National Institutes of Health, the National Science Foundation, the AmericanHeartAssociation, andthe Office ofNaval Research. Dr. Lemastersis the author ofover200 papersand has previouslyeditedtwo books. His current major research interests relate to ischemia/reperfusion injury and organ preservation for transplantation surgery. Constance Oliver, Ph.D., is a Program Officer in the Biomedical Science and Technology Program at the Office ofNaval Research (ONR), Arlington, Virginia. Prior to joining ONR she was a Research Biologist at the National Institute ofDentalResearch, the NationalInstitutesofHealth, Bethesda,Mary land. She received her B.A. degree from Northwestern University, Evanston, Illinois, her M.S. from the University ofUtah, Salt Lake City, Utah, and her Ph.D. from the University ofTexas at Austin, Austin, Texas. Dr. Oliverhas overtwenty years of experience in the field of cell biology. Her research has focused on structure-function relationships in the secretory pathway in exocrine acinarcellsandinmastcellsJ She has examinedpackaging ofsecretory proteins and formation ofsecretory granules, membrane traffick ing and signaltransductionmechanisms in thesecells. Currently,Dr. Oliver is managing researchprograms in Biomedical Science and Technology. She has publishedextensively and hasmadenumerouspresentations at local, national, and international conferences, workshops, and symposia based on her own research. In addition, she has editedseveral booksand conferenceproceedings and served on the editorial board of The Journal ofHistochemistry and Cy tochemistry. Dr. Oliver is a member of the American Society for Cell Biology, the Histochemical Society, the Microscopy Society of America, the American Association for the Advancement of Science, the Association for Women in Science, andthe Chesapeake Society ofElectronMicroscopy. Inaddition, she waselected to membershipin Sigma Xi, an honorary academic society, named an Outstanding Young Woman ofAmerica, 1977, andreceived a Gold Medal from Tokyo Dental College, 1984. CONTRIBUTORS Daniel Acosta, Jr., Ph.D. John D. Chen, M.D. College ofPharmacy Department ofDermatology University ofTexas Northwestern University School of Austin, Texas Medicine Chicago, Illinois Sigrid Bachmann, Ph.D. Department of Surgery Free University ofBerlin John A. Cidlowski, Ph.D. Germany Department ofPhysiology University ofNorth Carolina at John M. Bond, D.V.M., Ph.D. Chapel Hill Department of Cell Biology & Chapel Hill, North Carolina Anatomy University of North Carolina at Henry D. Connor, Ph.D. Chapel Hill Department ofPharmacology Chapel Hill, North Carolina University ofNorth Carolina at Chapel Hill Charles W. Broge, B.S. Department ofPharmacology and Chapel Hill, North Carolina Cell Biophysics University of Cincinnati College of Robert T. Currin, B.S. Medicine Department of Cell Biology & Cincinnati, Ohio Anatomy School ofMedicine Steven F. Bronk, B.S. University ofNorth Carolina at Department of Internal Medicine Chapel Hill Mayo Medical School Chapel Hill, North Carolina Rochester, Minnesota Wayne E. Cascio, M.D. Carla da Mouta, B.S. Department ofMedicine Transplantation Laboratory University ofNorth Carolina at American Red Cross Chapel Hill Jerome Holland Laboratory Chapel Hill, North Carolina Rockville, Maryland Enrique Chacon, Ph.D. Department of Cell Biology & Dipak K. Das, Ph.D. Anatomy Department of Surgery University ofNorth Carolina at University of Connecticut School of Chapel Hill Medicine Chapel Hill, North Carolina Farmington, Connecticut
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