Differential regulation of human and murine P-selectin expression and function in vivo
نویسندگان
چکیده
Leukocytes roll on P-selectin after its mobilization from secretory granules to the surfaces of platelets and endothelial cells. Tumor necrosis factor (TNF), IL-1β, and lipopolysaccharide increase synthesis of P-selectin in murine but not in human endothelial cells. To explore the physiological significance of this difference in gene regulation, we made transgenic mice bearing the human Selp gene and crossed them with mice lacking murine P-selectin (Selp(-/-)). The transgenic mice constitutively expressed human P-selectin in platelets, endothelial cells, and macrophages. P-selectin mediated comparable neutrophil migration into the inflamed peritoneum of transgenic and wild-type (WT) mice. Leukocytes rolled similarly on human or murine P-selectin on activated murine platelets and in venules of the cremaster muscle subjected to trauma. However, TNF increased murine P-selectin in venules, slowing rolling and increasing adhesion, whereas it decreased human P-selectin, accelerating rolling and decreasing adhesion. Both P- and E-selectin mediated basal rolling in the skin of WT mice, but E-selectin dominated rolling in transgenic mice. During contact hypersensitivity, murine P-selectin messenger (m) RNA was up-regulated and P-selectin was essential for leukocyte recruitment. However, human P-selectin mRNA was down-regulated and P-selectin contributed much less to leukocyte recruitment. These findings reveal functionally significant differences in basal and inducible expression of human and murine P-selectin in vivo.
منابع مشابه
DIFFERENTIAL EXPRESSION OF SURFACE MARKERS CD45RB AND CD44 ON MURINE CD8+ CELLS
Considering the emerging importance of phenotypic markers as indicators of cell function and differentiation, we studied patterns ofCD44 and CD45RB expression in CD8+ murine T cells with prior exposure to antigen or staphylococcal enterotoxin B ( SEB ). Following in vivo priming with two purified protein derivatives (one from a virulent WHO strain and the other from an avirulent strain), T ...
متن کاملInterferon Gamma Unresponsiveness Due to Down-Regulation of IFN-γR Expression in Experimental Cutaneous Leishmaniasis
It is now well documented that interferon gamma (IFN-γ) is the indispensable cytokine for inducing protective immunity against experimental and human cutaneous leishmaniaisis. The importance of IFN-γ receptor (IFN-γR) has also been studied. In the present study, we made attempts to find out whether L. major infection is able to alter the expression of IFN-γR in vivo. In addition, we studied the...
متن کاملReplacing the Promoter of the Murine Gene Encoding P-selectin with the Human Promoter Confers Human-like Basal and Inducible Expression in Mice.
In humans and mice, megakaryocytes/platelets and endothelial cells constitutively synthesize P-selectin and mobilize it to the plasma membrane to mediate leukocyte rolling during inflammation. TNF-α, interleukin 1β, and LPS markedly increase P-selectin mRNA in mice but decrease P-selectin mRNA in humans. Transgenic mice bearing the entire human SELP gene recapitulate basal and inducible express...
متن کاملEffect of Tribulus Terrestris L. on Expression of ICAM-1, VCAM-1, E-Selectin and Proteome Profile of Human Endothelial Cells In-Vitro
Background: Atherosclerosis is a chronic inflammation that interferes with blood arteries functions due to the accumulation of low density lipids and cholesterol. Objective: To investigate the effect of aqueous extract and saponin fraction of Tribulus terrestris L. (TT) on the proteome and expression of intracellular adhesion molecule-1 (ICAM-1), vascu...
متن کاملDown-Regulation of T Cell Function by Heat Shock-Induced Excretory Factor of Leishmania Major
Background: Despite demonstration of molecular and biochemical changes induced by heat shock on Leishmania, the immunological importance of such changes has not been elucidated. Objective: Studying the effect of two excretory factors prepared under heat shock and ambient temperature from Leishmania major on Balb/c splenocytes function. Methods: The parasites were cultured at 25°C and then sub...
متن کامل