Neuropeptides, via specific receptors, regulate T cell adhesion to fibronectin.
The ability of T cells to adhere to and interact with components of the blood vessel walls and the extracellular matrix is essential for their extravasation and migration into inflamed sites. We have found that the beta1 integrin-mediated adhesion of resting human T cells to fibronectin, a major glycoprotein component of the extracellular matrix, is induced by physiologic concentrations of three neuropeptides: calcitonin gene-related protein (CGRP), neuropeptide Y, and somatostatin; each acts via its own specific receptor on the T cell membrane. In contrast, substance P (SP), which coexists with CGRP in the majority of peripheral endings of sensory nerves, including those innervating the lymphoid organs, blocks T cell adhesion to fibronectin when induced by CGRP, neuropeptide Y, somatostatin, macrophage inflammatory protein-1beta, and PMA. Inhibition of T cell adhesion was obtained both by the intact SP peptide and by its 1-4 N-terminal and its 4-11, 5-11, and 6-11 C-terminal fragments, used at similar nanomolar concentrations. The inhibitory effects of the parent SP peptide and its fragments were abrogated by an SP NK-1 receptor antagonist, suggesting they all act through the same SP NK-1 receptor. These findings suggest that neuropeptides, by activating their specific T cell-expressed receptors, can provide the T cells with both positive (proadhesive) and negative (antiadhesive) signals and thereby regulate their function. Thus, neuropeptides may influence diverse physiologic processes involving integrins, including leukocyte-mediated migration and inflammation.
Levite
M
M
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Cahalon
L
L
Hershkoviz
R
R
Steinman
L
L
Lider
O
O
D000276:Adjuvants, Immunologic / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D054407:Chemokine CCL4; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D007424:Intracellular Fluid / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013004:Somatostatin / Q000494:pharmacology; D013373:Substance P / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D054407:Chemokine CCL4; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D019402:Macrophage Inflammatory Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D018015:Receptors, Calcitonin Gene-Related Peptide; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D018040:Receptors, Neurokinin-1; D018013:Receptors, Neuropeptide; D017476:Receptors, Neuropeptide Y; D017481:Receptors, Somatostatin; D013373:Substance P; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide; D013755:Tetradecanoylphorbol Acetate