Human C1R peptide

The exact mechanism of the cardiotoxic actions of cocaine remains unclear. The finding that the heart may be a source of injurious complement components led us to investigate whether cocaine promotes myocardial expression of complement. Rabbit isolated hearts were perfused for 70 min with either cocaine hydrochloride (1 or 10 mu M), the synthetic isomer (+)-cocaine (10 mu M), or procaine hydrochloride (10 or 30 mu M). Compared with controls perfused with drug-free buffer, both cocaine and procaine significantly (P<.05) increased myocardial C1q, C1r, C8, and C9 mRNA expression, whereas 10 mu M (+)-cocaine had no effect on complement mRNA expression. Cocaine also significantly increased (P<.05) C3 mRNA transcription. In addition, in vivo administration of cocaine (1 mg/kg) for three consecutive days significantly increased myocardial complement mRNA expression. Cocaine and procaine also increased membrane attack complex (MAC) formation in the myocardium. The antioxidant 2-N-mercaptopropionyl glycine, attenuated the increases in complement mRNA expression induced by 1 mu M cocaine and 10 mu M procaine. In vivo heparin administration (300 U/kg i.v.), 2 h before removal of the heart and exposure to 1 mM cocaine, did not inhibit C1q, C1r, C3, and C8 mRNA transcription, but decreased MAC expression. It was determined previously that heparin reduces myocardial ischemia/reperfusion injury. Our results suggest that cocaine may cause myocardial injury by up-regulating local complement expression, possibly via the production of reactive oxygen species. Furthermore, the glycosaminoglycan heparin may modulate the cytotoxic effects of cocaine by impeding formation of the MAC.

gamma delta T cells are present in the mucosal intestinal epithelia and secrete factors necessary to maintain tissue integrity. Ags recognized by these cells are poorly defined, although in mice non-classical MHC class I molecules have been implicated. Since MHC class I-like CD1 receptors are widely expressed at the surface of epithelial and dendritic intestinal cells and have the capacity to present lipid Ags to T cells, we hypothesized that these molecules might present autologous and/or exogenous phospholipids to intestinal gamma delta T lymphocytes. Intraepithelial T lymphocytes from normal human duodenal mucosal biopsies were cloned and exposed to natural and synthetic phospholipids using CD1a-, CD1b-, CD1c- or CD1d-transfected C1R lymphoblastoid or HeLa cell lines as APCs. Their cytolytic properties and regulatory cytokine secretion were also examined. Most clones obtained from duodenal mucosa (up to 70%) were TCR alpha beta(+), and either CD4(+) or CD8(+), whereas 20% were CD4(-)CD8(-) (6 clones) or TCR gamma delta(+) (12 clones). A relevant percentage (up to 66%) of TCR gamma delta(+) but few (< 5%) TCR alpha beta(+) T cell clones responded to synthetic and/or natural phospholipids presented by CD1 molecules, as measured by both [H-3]thymidine incorporation and IL-4 release assays. A Th1-like cytolytic and functional activity along with the ability to secrete regulatory cytokines was observed in most phospholipid-specific gamma delta T cell clones. Thus, a substantial percentage of TCR gamma delta(+) but few TCR alpha beta(+) from human duodenal mucosa recognize exogenous phospholipids in a CD1-restricted fashion. This adaptive response could contribute to mucosal homeostasis, but could also favor the emergence of inflammatory or allergic intestinal diseases.