Abstract
The interaction of leukocytes with the vessel endothelium to facilitate the extravasation into the tissue represents a key process of the bodys defense mechanisms. Excessive recruitment of leukocytes into the inflamed tissue in chronic diseases like autoimmune disorders could be prevented by interfering with the mechanisms of leukocyte extravasation. Significant progress in elucidating the molecular basis of the trafficking of leukocytes from the blood stream to the extravascular tissue has been achieved that enables new strategies for therapeutic approaches. The multistep process of leukocyte rolling, firm adhesion and transmigration through the endothelial wall is facilitated by a dynamic interplay of adhesion receptors on both leukocytes and endothelial cells as well as chemokines. In preclinical studies using various animal models, promising results have been received demonstrating that blocking of adhesion receptors of the selectin and integrin families improved the inflammation process in models of ulcerative colitis, autoimmune encephalomyelitis or contact hypersensitivity. In addition to the targeting of adhesion receptors by antibodies, small molecules that mimic epitopes of adhesion receptor ligands have been developed and successfully applied in animal models. Clinical studies revealed a limited response using antibodies to selectins or LFA-1 integrins compared with animal models. However, using humanized antibodies to the α4- integrin subunit significant efficacy has been demonstrated in autoimmune diseases like psoriasis, multiple sclerosis and inflammatory bowel disease.
Keywords: Autoimmune disease, integrin, leukocyte, endothelium, rolling, adhesion receptors, inflammation, antibody therapy
Current Pharmaceutical Design
Title: Therapeutic Strategies in Autoimmune Diseases by Interfering with Leukocyte Endothelium Interaction
Volume: 12 Issue: 29
Author(s): Joachim Rychly and Barbara Nebe
Affiliation:
Keywords: Autoimmune disease, integrin, leukocyte, endothelium, rolling, adhesion receptors, inflammation, antibody therapy
Abstract: The interaction of leukocytes with the vessel endothelium to facilitate the extravasation into the tissue represents a key process of the bodys defense mechanisms. Excessive recruitment of leukocytes into the inflamed tissue in chronic diseases like autoimmune disorders could be prevented by interfering with the mechanisms of leukocyte extravasation. Significant progress in elucidating the molecular basis of the trafficking of leukocytes from the blood stream to the extravascular tissue has been achieved that enables new strategies for therapeutic approaches. The multistep process of leukocyte rolling, firm adhesion and transmigration through the endothelial wall is facilitated by a dynamic interplay of adhesion receptors on both leukocytes and endothelial cells as well as chemokines. In preclinical studies using various animal models, promising results have been received demonstrating that blocking of adhesion receptors of the selectin and integrin families improved the inflammation process in models of ulcerative colitis, autoimmune encephalomyelitis or contact hypersensitivity. In addition to the targeting of adhesion receptors by antibodies, small molecules that mimic epitopes of adhesion receptor ligands have been developed and successfully applied in animal models. Clinical studies revealed a limited response using antibodies to selectins or LFA-1 integrins compared with animal models. However, using humanized antibodies to the α4- integrin subunit significant efficacy has been demonstrated in autoimmune diseases like psoriasis, multiple sclerosis and inflammatory bowel disease.
Export Options
About this article
Cite this article as:
Rychly Joachim and Nebe Barbara, Therapeutic Strategies in Autoimmune Diseases by Interfering with Leukocyte Endothelium Interaction, Current Pharmaceutical Design 2006; 12 (29) . https://dx.doi.org/10.2174/138161206778559696
DOI https://dx.doi.org/10.2174/138161206778559696 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Adult Stem Cells for Cartilage Tissue Engineering and Regeneration
Current Rheumatology Reviews Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Antagonists in Experimental Myocarditis
Current Pharmaceutical Design Neurotrophins - From Pathophysiology to Treatment in Alzheimers Disease
Current Alzheimer Research Towards Retinoid Therapy for Alzheimers Disease
Current Alzheimer Research Distribution of Podoplanin in Synovial Tissues in Rheumatoid Arthritis Patients Using Biologic or Conventional Disease-Modifying Anti-Rheumatic Drugs
Current Rheumatology Reviews Viral Encephalitis: Current Treatments and Future Perspectives
Central Nervous System Agents in Medicinal Chemistry Specific Immune Intervention with Monoclonal Antibodies for the Treatment of Multiple Sclerosis
Current Medicinal Chemistry Targeting Kinin Receptors for the Treatment of Neurological Diseases
Current Pharmaceutical Design “Self-Nonself” Peptides in the Design of Vaccines
Current Pharmaceutical Design New Insights into the Modulation of Immune Response by Fasciola hepatica Excretory-Secretory Products
Current Immunology Reviews (Discontinued) Possible Pathomechanisms Responsible for Injury to the Central Nervous System in the Settings of Chronic Cerebrospinal Venous Insufficiency
Reviews on Recent Clinical Trials Th17 and Treg Cells, Two New Lymphocyte Subpopulations with a Key Role in the Immune Response Against Infection
Infectious Disorders - Drug Targets Editorial: [Hot Topic: Keeping Track of an Expanding Subject - Recent Trends in Immunology and their Clinical Implications]
Current Pharmaceutical Design CCR1 Antagonists: What Have We Learned From Clinical Trials
Current Topics in Medicinal Chemistry Targeted Drug Delivery to Central Nervous System (CNS) for the Treatment of Neurodegenerative Disorders: Trends and Advances
Central Nervous System Agents in Medicinal Chemistry Curcuminoids in Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Selective Elevation of Circulating CCL2/MCP1 Levels in Patients with Longstanding Post-vaccinal Macrophagic Myofasciitis and ASIA
Current Medicinal Chemistry Are Circulating Monocytes as Microglia Orthologues Appropriate Biomarker Targets for Neuronal Diseases? (Supplementry Table)
Central Nervous System Agents in Medicinal Chemistry Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy
Current Pharmaceutical Design Modulation of T Cell Proliferation Through the LIGHT-HVEM-BTLA Cosignaling Pathway
Recent Patents on DNA & Gene Sequences