THE BIOLOGY AND PATHOLOGY OF INNATE IMMUNITY MECHANISMS ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY EditorialBoard: NATHAN BACK, State University of New York at Buffalo IRUNR.COHEN,The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume470 COLON CANCER PREVENTION: Dietary Modulation of Cellular and Molecular Mechanisms Edited under the auspices of the American Institute for Cancer Research Volume471 OXYGEN TRANSPORT TO TISSUE XXI Edited by Andras Eke and David T. Delpy Volume472 ADVANCES IN NUTRITION AND CANCER 2 Edited by Vincenzo Zappia, Fulvio Della Ragione, Alfonso Barbarisi, Gian Luigi Russo, and Rossano Dello Iacovo Volume473 MECHANISMS IN THE PATHOGENESIS OF ENTERIC DISEASES 2 Edited by Prem S. Paul and David H. Francis Volume474 HYPOXIA: Into the Next Millennium Edited by Robert C. Roach, Peter D. Wagner, and Peter H. Hackett Volume475 OXYGEN SENSING: Molecule to Man Edited by Sukhamay Lahiri, Nanduri R. Prabhakar, and Robert E. Forster, II Volume476 ANGIOGENESIS: FromtheMolecular toIntegrative Pharmacology Edited by Michael E. Maragoudakis Volume477 CELLULAR PEPTIDASES INIMMUNE FUNCTIONS ANDDISEASES 2 Edited by Jürgen Langner and Siegfried Ansorge Volume478 SHORT AND LONG TERM EFFECTS OFBREAST FEEDING ONCHILD HEALTH Edited byBerthold Koletzko, OlleHernell, and Kim Fleischer Michaelsen Volume479 THEBIOLOGY ANDPATHOLOGY OFINNATE IMMUNITY MECHANISMS Edited byYona Keisari and Itzhak Ofek A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. THE BIOLOGY AND PATHOLOGY OF INNATE IMMUNITY MECHANISMS Edited by YonaKeisari and Itzhak Ofek Sackler Faculty of Medicine Tel Aviv University Tel Aviv, Israel KLUWER ACADEMIC PUBLISHERS New York, Boston, Dordrecht, London, Moscow (cid:72)(cid:37)(cid:82)(cid:82)(cid:78)(cid:44)(cid:54)(cid:37)(cid:49)(cid:29) 0-306-46831-X (cid:51)(cid:85)(cid:76)(cid:81)(cid:87)(cid:3)(cid:44)(cid:54)(cid:37)(cid:49)(cid:29) 0-306-46409-8 (cid:139)(cid:21)(cid:19)(cid:19)(cid:21)(cid:3)(cid:46)(cid:79)(cid:88)(cid:90)(cid:72)(cid:85)(cid:3)(cid:36)(cid:70)(cid:68)(cid:71)(cid:72)(cid:80)(cid:76)(cid:70)(cid:3)(cid:51)(cid:88)(cid:69)(cid:79)(cid:76)(cid:86)(cid:75)(cid:72)(cid:85)(cid:86) (cid:49)(cid:72)(cid:90)(cid:3)(cid:60)(cid:82)(cid:85)(cid:78)(cid:15)(cid:3)(cid:37)(cid:82)(cid:86)(cid:87)(cid:82)(cid:81)(cid:15)(cid:3)(cid:39)(cid:82)(cid:85)(cid:71)(cid:85)(cid:72)(cid:70)(cid:75)(cid:87)(cid:15)(cid:3)(cid:47)(cid:82)(cid:81)(cid:71)(cid:82)(cid:81)(cid:15)(cid:3)(cid:48)(cid:82)(cid:86)(cid:70)(cid:82)(cid:90) (cid:36)(cid:79)(cid:79)(cid:3)(cid:85)(cid:76)(cid:74)(cid:75)(cid:87)(cid:86)(cid:3)(cid:85)(cid:72)(cid:86)(cid:72)(cid:85)(cid:89)(cid:72)(cid:71) (cid:49)(cid:82)(cid:3)(cid:83)(cid:68)(cid:85)(cid:87)(cid:3)(cid:82)(cid:73)(cid:3)(cid:87)(cid:75)(cid:76)(cid:86)(cid:3)(cid:72)(cid:37)(cid:82)(cid:82)(cid:78)(cid:3)(cid:80)(cid:68)(cid:92)(cid:3)(cid:69)(cid:72)(cid:3)(cid:85)(cid:72)(cid:83)(cid:85)(cid:82)(cid:71)(cid:88)(cid:70)(cid:72)(cid:71)(cid:3)(cid:82)(cid:85)(cid:3)(cid:87)(cid:85)(cid:68)(cid:81)(cid:86)(cid:80)(cid:76)(cid:87)(cid:87)(cid:72)(cid:71)(cid:3)(cid:76)(cid:81)(cid:3)(cid:68)(cid:81)(cid:92)(cid:3)(cid:73)(cid:82)(cid:85)(cid:80)(cid:3)(cid:82)(cid:85)(cid:3)(cid:69)(cid:92)(cid:3)(cid:68)(cid:81)(cid:92)(cid:3)(cid:80)(cid:72)(cid:68)(cid:81)(cid:86)(cid:15)(cid:3)(cid:72)(cid:79)(cid:72)(cid:70)(cid:87)(cid:85)(cid:82)(cid:81)(cid:76)(cid:70)(cid:15) (cid:80)(cid:72)(cid:70)(cid:75)(cid:68)(cid:81)(cid:76)(cid:70)(cid:68)(cid:79)(cid:15)(cid:3)(cid:85)(cid:72)(cid:70)(cid:82)(cid:85)(cid:71)(cid:76)(cid:81)(cid:74)(cid:15)(cid:3)(cid:82)(cid:85)(cid:3)(cid:82)(cid:87)(cid:75)(cid:72)(cid:85)(cid:90)(cid:76)(cid:86)(cid:72)(cid:15)(cid:3)(cid:90)(cid:76)(cid:87)(cid:75)(cid:82)(cid:88)(cid:87)(cid:3)(cid:90)(cid:85)(cid:76)(cid:87)(cid:87)(cid:72)(cid:81)(cid:3)(cid:70)(cid:82)(cid:81)(cid:86)(cid:72)(cid:81)(cid:87)(cid:3)(cid:73)(cid:85)(cid:82)(cid:80)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:51)(cid:88)(cid:69)(cid:79)(cid:76)(cid:86)(cid:75)(cid:72)(cid:85) (cid:38)(cid:85)(cid:72)(cid:68)(cid:87)(cid:72)(cid:71)(cid:3)(cid:76)(cid:81)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:56)(cid:81)(cid:76)(cid:87)(cid:72)(cid:71)(cid:3)(cid:54)(cid:87)(cid:68)(cid:87)(cid:72)(cid:86)(cid:3)(cid:82)(cid:73)(cid:3)(cid:36)(cid:80)(cid:72)(cid:85)(cid:76)(cid:70)(cid:68) (cid:57)(cid:76)(cid:86)(cid:76)(cid:87)(cid:3)(cid:46)(cid:79)(cid:88)(cid:90)(cid:72)(cid:85)(cid:3)(cid:50)(cid:81)(cid:79)(cid:76)(cid:81)(cid:72)(cid:3)(cid:68)(cid:87)(cid:29)(cid:3)(cid:3) (cid:75)(cid:87)(cid:87)(cid:83)(cid:29)(cid:18)(cid:18)(cid:90)(cid:90)(cid:90)(cid:17)(cid:78)(cid:79)(cid:88)(cid:90)(cid:72)(cid:85)(cid:82)(cid:81)(cid:79)(cid:76)(cid:81)(cid:72)(cid:17)(cid:70)(cid:82)(cid:80) (cid:68)(cid:81)(cid:71)(cid:3)(cid:46)(cid:79)(cid:88)(cid:90)(cid:72)(cid:85)(cid:10)(cid:86)(cid:3)(cid:72)(cid:37)(cid:82)(cid:82)(cid:78)(cid:86)(cid:87)(cid:82)(cid:85)(cid:72)(cid:3)(cid:68)(cid:87)(cid:29) (cid:75)(cid:87)(cid:87)(cid:83)(cid:29)(cid:18)(cid:18)(cid:90)(cid:90)(cid:90)(cid:17)(cid:72)(cid:69)(cid:82)(cid:82)(cid:78)(cid:86)(cid:17)(cid:78)(cid:79)(cid:88)(cid:90)(cid:72)(cid:85)(cid:82)(cid:81)(cid:79)(cid:76)(cid:81)(cid:72)(cid:17)(cid:70)(cid:82)(cid:80) Preface In recent years increased scientific attention has been given to immediate defense mechanisms based on non-clonal recognition of microbial components. These mechanisms constitute the innate immunity arm of the body's defense. Identification of pathogens by these mechanisms involves primarily receptors recognizing sugar moieties of various microorganisms. Innate immunity based mechanisms are essential for the existence of multicellular organisms. They are evolutionarily conserved and designed to provide immediate protection against microbial pathogens to eradicate infection. Activation of innate immunity is crucial for transition to specific immunity and for its orientation, and to assist the specific immune response in the recognition of pathogens and their destruction. Innate immunity is regularly involved in the arrest of bacterial, mycotic, viral and parasitic infections, giving the specific immune response time to become effective. It becomes critically essential in immunocompromised patients who fail to mount specific immune responses due to congenital or acquired immunodeficiencies as a result of chemotherapy, dialysis, immunosuppressive drugs, or HIV infection. The Innate Immunity arsenal constitutes polymorphonuclear and mononuclear phagocytes, mast cells, the complement system, Natural Killer cells, antimicrobial peptides, and presumably a subset of T lymphocytes with TCRl receptors. This book includes manuscripts of lectures presented at the "Bat Sheva Seminar on Innate Immunity" held in Israel, October 1999. The major topics presented and discussed in the seminar included (i) the role of innate immune responses as a first line defense against microbial infection, and v Preface vi tumor cells; (ii) the cellular and molecular basis of the function of cells and molecules involved in innate immunity; (iii) the role of innate immunity in the immunocompromised host; and (iv) the interactions between innate immunity components and clonal immune response. This book includes the major themes of this rapidly developing area; however, we by no means intend to cover all aspects of innate immunity. The book's first section deals with receptors, lectins and collectins with emphasis on interaction of these molecules with pathogens. The second section deals with the arsenal of host cells and cytokines playing crucial roles in innate immunity, and the third section is devoted to aspects of antimicrobial peptides. Because of its special importance, innate immunity in the compromised host is the focus of the next section. The last section deals with the interrelationship of innate immunity components and tumor cells. In order to expand the scope of the volume even further, we have also included the abstracts of some of the lectures and posters presented during the seminar. We thank the authors for their collaborative efforts. We also trust that the highlights of this book will stimulate new ideas that lead to practical designs for better understanding the complex interactions of components of the innate immunity in order to develop effective agents and measures for preventing or treating infectious diseases and malignancies. We would like to express our gratitude to all our colleagues and friends, especially to the members of the Organizing Committee (E. Ezekowitz, S. Gordon, M. Fridkin, M. Shapira, A. Mantovani, E. Yefenof, A. Etzioni and N. Sharon) who suggested, argued and altogether helped a great deal, and in many ways allowed the seminar to bloom. We believe that a follow-up seminar should be held to present and discuss the results of the new ideas that were illuminated here. Itzhak Ofek and Yonka Keisari, Chairpersons. Contents I. PATTERN RECOGNITION, RECEPTORS AND COLLECTINS IN INNATE IMMUNITY 1. Mannose receptor and scavenger receptor: two macrophage pattern recognition receptors with diverse functions in tissue homeostasis and host defense S. A. Linehan, L. Martinez-Pomares, and S. Gordon..............................1 2. Complement receptor 3 (CR3): a public transducer of innate immunity signals in macrophages E. Yefenof..............................................................................................15 3. The role ofC-type lectins in the innate immunity against pulmonary pathogens I. Ofek, E. Crouch, and Y. Keisari.......................................................27 4. Modulation of nitric oxide production by lung surfactant in alveolar macrophages M. Kalina, H. Blau, S. Riklis, and V. Hoffman.....................................37 5. Development of chimeric collectins with enhanced activity against influenza A virus K. L. Hartshorn, M. R. White, R. A. B. Ezekowitz, K. Sastry, and E. Crouch .........................................................................................49 vii Contents viii 6. Initial steps in Streptococcus pneumoniae interaction with and pathogenicity to the host M. Shani-Sekler, S. Lifshitz, I. Hillel, R. Dagan, N. Grossman, G. Fleminger, and Y. Mizrachi-Brauner................................................61 11. HOST CELLS AND CYTOKINES IN INNATE IMMUNITY 7. Role of cytokines in the maturation and function of macrophages: effect of GM-CSF and IL-4 Y. Keisari, G. Robin, L. Nissimov, H. Wang, A. Mesika, R. Dimri, and I. Ofek.............................................................................................73 8. Mast cell modulation of the innate immune response to enterobacterial infection S. N. Abraham and R. Malaviya...........................................................91 9. The NADPH oxidase diaphorase activity in permeabilized human neutrophils and granulocytic like PLB-985 cells I. Pessach and R. Levy ........................................................................107 10. Activation of cytosolic phospholipase A by opsonized 2 zymosan in human neutrophils requires both ERK and p38 MAP-kinase I. Hazan-Halevy and R. Levy...............................................................115 11. Cytosolic phospholipase A is required for the activation ofthe 2 NADPH oxidase associated H+channel in phagocyte-like cells R. Levy, A. Lowenthal, and R. Dana...................................................125 12. The role of NK cells in innate immunity N. Lieberman and 0. Mandelboim ......................................................137 13. Similarities and dissimilarities between humans and mice looking at adhesion molecules defects A. Etzioni, C. M. Doerschuk, and J. M. Harlan....................................147 14. The role ofdendritic cells at the early stagesof Leishmania infection H. Moll ................................................................................................163 15. DNA-based vaccines: the role of dendritic cells in antigen presentation L. Paul and A. Porgador......................................................................175 Contents ix α β 16. Distinct patterns ofIL- 1 and IL-1 organ distribution– a possible basis for organ mechanisms of innate immunity M. Hacham, S. Argov, R. M. White, S. Segal, andR. N. Apte......185 III. ANTIMICROBIALPEPTIDES 17. Structure and biology of cathelicidins M. Zanetti, R. Gennaro, M. Scocchi, and B. Skerlavaj ...................203 18. Structure activity relationship study of polymyxin B nonapeptide H. Tsubery, I. Ofek, S. Cohen, and M. Fridkin....................................219 IV. INNATE IMMUNITY IN THE COMPROMISED HOST 19. The clinical significance of neutrophil dysfunction B. Wolach, R. Gavrieli, and D. Ross .................................................223 20. Clinical significance of functional aberrations in macrophage and NK cells, in type-1 cytokines and in lectin-binding molecules Z. Handzel ............................................................................................227 21. Klebsiella infections in the immunocompromised host H. Sahly, R. Podschun, and U. Ullmann.............................................237 V. INNATE IMMUNITY COMPONENTS IN CANCER 22. Macrophage – recognized molecules of apoptotic cells are expressed at higher levels in AKR lymphoma of aged as compared to young mice O. Itzhaki, E. Skutelsky, T. Kaptzan, A. Siegal, M. Michowitz, J. Sinai, M. Huszar, S. Nafar, and J. Leibovici..................................251 23. Sensitivity to macrophages decreases with tumor progression in the AKR lymphoma T. Kaptzan, E. Skutelsky, M. Michowitz, A. Siegal, O. Itzhaki, S. Hoenig, J. Hiss, S. Kay, and J. Leibovici ....................................263 X Contents α β 24. Opposing effects of IL-1 and IL-1 on malignancy α patterns: Tumor cell-associated IL-1 potentiates anti-tumor β immune responses and tumor regression, whereas IL-1 potentiates invasiveness R. N. Apte, T. Dvorkin, X. Song, E. Fima, Y. Krelin, A. Yulevitch, R. Gurfinkel, A. Werman, R. M. White, S. Argov, Y. Shendler, 0. Bjorkdahl, M. Dohlsten, M. Zoller, S. Segal, and E. Voronov ...................................................................277 25. Abstracts ..............................................................................................289 26. Index....................................................................................................323