Thrombin enhances T cell proliferative responses and cytokine production.
Human alpha-thrombin, in addition to its procoagulant activity, is a mitogen for fibroblasts and endothelial cells and a chemotactic agent for monocytes. To further understand the complex physiological functions of thrombin, we investigated whether thrombin has any immunoregulatory function with regard to T cell activation. Using highly purified human alpha-thrombin and peripheral blood mononuclear cells (PBMC), we investigated whether thrombin has any effect on cytokine production and/or proliferation induced by different T cell stimuli. At physiological concentrations (1-10 micrograms/ml, 30-300 nM), thrombin significantly enhances T cell proliferation in response to mitogens, superantigens, alloantigens, and anti-CD3 stimulation. Enhanced proliferation was associated with increased IL2 and IL6 production and with an increase in the number of IL2r+ (CD25)-bearing T cells. Thrombin alone was not mitogenic nor did it induce IL2 production or increase the number of IL2r+ T cells. However, PBMC exposed to thrombin alone produced high levels of IL6. Thrombin also enhanced IL2-induced proliferation of murine and human IL2-dependent cell lines. These results suggest that thrombin may play an important role in regulating cell-mediated immunity.
Naldini
A
A
Institute of General Physiology, University of Siena, Italy.
Carney
D H
DH
Bocci
V
V
Klimpel
K D
KD
Asuncion
M
M
Soares
L E
LE
Klimpel
G R
GR
D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology*
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D013917:Thrombin