ABSTRACT
The vaccinia virus complement control protein (VCP) possesses multiple modulatory functions. Functioning as a complement inhibitory protein, VCP reduces production of proinflammatory chemotactic factors produced during complement activation. Additionally, VCP binds heparin and heparan sulfate proteoglycans, resulting in added functions shown to block monocyte chemotaxis in vitro. Using an in vivo spinal cord contusive injury model in rats, the inflammation-modulating abilities of VCP were evaluated. The results of both myeloperoxidase assaying and H&E stained section counts of spinal tissue reveal that neutrophil infiltration to the area of the lesion was reduced in animals that received VCP as compared to saline-injected controls.
Subject(s)
Inflammation/therapy , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/therapy , Viral Proteins/physiology , Animals , Disease Models, Animal , Inflammation/etiology , Inflammation/pathology , Injections, Spinal , Peroxidase/metabolism , Rats , Rats, Sprague-Dawley , Spinal Cord Injuries/pathology , Viral Proteins/administration & dosageABSTRACT
Vaccinia virus complement control protein (VCP) has been shown to possess the ability to inhibit both classical and alternative complement pathway activation. The newly found ability of this protein to bind to heparin has been shown in previous studies to result in uptake by mast cells, possibly promoting tissue persistence. It has also been shown to reduce chemotactic migration of leukocytes by blocking chemokine binding. In addition, this study shows that VCP-through its ability to bind to glycosaminoglycans (heparin-like molecules) on the surface of human endothelial cells-is able to block antibody binding to surface major histocompatibility complex class I molecules. Since heparin binding is critical for many functions of this protein, we have attempted to characterize the molecular basis for this interaction. Segments of this protein, generated by genetic engineering of the DNA encoding VCP into the Pichia pastoris expression system, were used to localize the regions with heparin binding activity. These regions were then analyzed to more specifically define their properties for binding. It was found that the number of putative binding sites (K/R-X-K/R), the overall positive charge, and the percentage of positively charged amino acids within the protein were responsible for this interaction.
Subject(s)
Conserved Sequence , Endothelium, Vascular/immunology , Endothelium, Vascular/metabolism , Heparin/metabolism , Poxviridae/immunology , Viral Proteins/chemistry , Viral Proteins/metabolism , Amino Acid Motifs , Amino Acid Sequence , Antibodies, Monoclonal/immunology , Binding Sites , Complement Inactivator Proteins/chemistry , Complement Inactivator Proteins/genetics , Complement Inactivator Proteins/immunology , Complement Inactivator Proteins/metabolism , Endothelium, Vascular/cytology , Hemolysis , Histocompatibility Antigens Class I/immunology , Humans , Models, Molecular , Molecular Sequence Data , Poxviridae/chemistry , Poxviridae/genetics , Protein Binding , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Deletion/genetics , Static Electricity , Structure-Activity Relationship , Surface Properties , Viral Proteins/genetics , Viral Proteins/immunologyABSTRACT
Free erythrocyte protoporphyrin (FEP) and hemoglobin (Hgb) concentrations were tested in 790 children in a private pediatric office; results were compared to those obtained in 1984. Only 16 children (2%) had abnormal FEPs in 1990 compared to 76 children (9.6%) in the earlier study. The mean FEP in the normal group also decreased significantly in each age group studied. The hemoglobin concentrations were not significantly different in most of the age groups studied. Screening for iron deficiency in our pediatric practice by determining hemoglobin and FEP concentrations had a much lower yield in 1990 than in 1984.
Subject(s)
Erythrocytes/chemistry , Hemoglobins/analysis , Porphyrins/blood , Child , Child, Preschool , Humans , Infant , Reference ValuesABSTRACT
Virginia physicians administering preparticipation physicals to high school athletes this fall are using the new, expanded examination form that appears in this issue. Representing multidisciplinary input and incorporating current sports medicine information, the form is designed to identify the student at high risk for injury and to evaluate for a specific sport. After a two-year pilot program conducted by the authors the new form was officially adopted by the Virginia High School League.
