Combinatorial signals by inflammatory cytokines and chemokines mediate leukocyte interactions with extracellular matrix
| Autor: | Rami Hershkoviz, Ofer Lider, Alexander Brill, Iris Hecht, Hagai Schor, Liora Cahalon, Susanne Franitza, Gayle G. Vaday |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Chemokine
Stromal cell medicine.medical_treatment Immunology Proinflammatory cytokine Extracellular matrix Interferon-gamma Transforming Growth Factor beta medicine Cell Adhesion Leukocytes Immunology and Allergy Humans Secretion Chemokine CCL4 Chemokine CCL5 Cells Cultured Microscopy Video biology Chemotactic Factors Tumor Necrosis Factor-alpha Interleukins Granulocyte-Macrophage Colony-Stimulating Factor Chemotaxis Drug Synergism Cell Biology Macrophage Inflammatory Proteins Chemokine CXCL12 Cell biology Extracellular Matrix Fibronectins Chemotaxis Leukocyte Cytokine Matrix Metalloproteinase 9 biology.protein Cytokines Tumor necrosis factor alpha Laminin Chemokines Chemokines CXC Signal Transduction |
| Zdroj: | ResearcherID |
| ISSN: | 0741-5400 |
| Popis: | On their extravasation from the vascular system into inflamed tissues, leukocytes must maneuver through a complex insoluble network of molecules termed the extracellular matrix (ECM). Leukocytes navigate toward their target sites by adhering to ECM glycoproteins and secreting degradative enzymes, while constantly orienting themselves in response to specific signals in their surroundings. Cytokines and chemokines are key biological mediators that provide such signals for cell navigation. Although the individual effects of various cytokines have been well characterized, it is becoming increasingly evident that the mixture of cytokines encountered in the ECM provides important combinatorial signals that influence cell behavior. Herein, we present an overview of previous and ongoing studies that have examined how leukocytes integrate signals from different combinations of cytokines that they encounter either simultaneously or sequentially within the ECM, to dynamically alter their navigational activities. For example, we describe our findings that tumor necrosis factor (TNF)-α acts as an adhesion-strengthening and stop signal for T cells migrating toward stromal cell-derived factor-1α, while transforming growth factor-β down-regulates TNF-α-induced matrix metalloproteinase-9 secretion by monocytes. These findings indicate the importance of how one cytokine, such as TNF-α, can transmit diverse signals to different subsets of leukocytes, depending on its combination with other cytokines, its concentration, and its time and sequence of exposure. The combinatorial effects of multiple cytokines thus affect leukocytes in a step-by-step manner, whereby cells react to cytokine signals in their immediate vicinity by altering their adhesiveness, directional movement, and remodeling of the ECM. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text