We have isolated genomic clones encoding ITGAD partial, a new β2-integrin α subunit. Β2 integrin family in ITGAD gene, the deduced amino acid sequence is highly homologous to the gene encoding is known the α subunit from the previous three that make up the mapping of the position and intron / exon structure.

Acute administration of the monoclonal antibodies raised against a subset of leukocytes CD11d/CD18 integrins CD11d after spinal cord injury in rats improves neurological outcome considerably. This is due to reduced infiltration of neutrophils to spinal cord injury in rats primarily. More recently, the treatment of mice spinal cord injury, antibody decreases damaging the neurological recovery has been proven LY-6G neutrophils. The results of these different, there is a possibility for the difference in the inflammatory response of mice and rats due to the mechanism of action is different from using the two antibodies, or induced by SCI. Since the anti-CD11d treatment to deal with whether there is an effect in mice, and was intravenously administered in compression 24,2 any of fourth thoracic spine segment, control monoclonal antibody or CD11d monoclonal antibodies, 48 ​​hours 8-G damage was after. Myeloperoxidase activity, reactive oxygen species, lipid peroxidation, and anti-CD11d treatment reduces scarring reduce the infiltration of neutrophils in damaged spinal cord, the mouse is associated with increased protein sparing. Accompanied by increased serotonin immunoreactivity below the level of injury, these improvements in the microenvironment of the spinal cord that is damaged is to strengthen the recovery engine. Our results, in a rat model of SCI, 205C is, CD11d complement the previous work of monoclonal antibody treatment with the anti-integrin therapy.

You can fault constitutes the majority of traumatic brain injury, will lead the accumulation of damage, neurodegenerative disease, chronic neurological abnormalities. It remains the basic mechanism of these side effects are not well understood, there is no cure concrete for concussion now. The nerve inflammation, taking part in the cumulative nature of concussion more than one is suggested, he has contributed significantly to the secondary damage of knowledge after the recent and TBI, severe from our laboratory. Anti-CD11d monoclonal antibody that blocks CD11d/CD18 adhesion molecules react with integrin TBI after severe previously been found to reduce tissue damage experimental neuroinflammation, and oxidation activity and enhance functional recovery we. As may be involved in concussion repeated such treatment, we examined the effect of anti-CD11d process in the rat model of concussion to be repeated here.

The leukocyte integrin gene CD11d is expressed predominantely on subsets of the myelomonocytic lineage (myeloid cells), particularly on macrophage foam cells and splenic red pulp macrophages. Its expression pattern clearly differs from myeloid-specific leukocyte integrins CD11b and CD11c and the leukocyte-specific integrin CD11a. Although the functions of CD11d have not been determined in any detail, its expression in these cell types suggests that it may play a role in the atherosclerotic process. To better understand how this gene is regulated, the steady-state level of CD11d mRNA in differentiating bone marrow CD34+CD38- cells, peripheral blood monocytes, and monocytic cell lines was assessed by Northern blot analysis and RT-PCR and compared with those of CD11a, CD11b, and CD11c. Expression of CD11d occurs early in CD34+CD38- cells, rises, and then decreases, in contrast to the expression of the other leukocyte integrins. Expression of CD11d reappears in peripheral blood monocytes differentiating to macrophage foam cells. Oxidized lipoproteins (OxLDL) and acetylated lipoproteins (AcLDL) failed to upregulate CD11d following differentiation of peripheral blood monocytes or the monocytic cell line HL60. However, when both OxLDL and AcLDL were present during differentiation, CD11d was further upregulated. This suggests that expression of CD11d is coordinately regulated with expression of LDL receptors and the development of the foam cell. Site-directed mutagenesis of the -100 to -20 region of the CD11d promoter revealed transcription factor binding sites essential for expression of this gene. Decoy oligonucleotides to the -100 to -20 region taken up by CD34+CD38- cells block their differentiation into myeloid colonies. This suggests that one or more transcription factors that regulate CD11d also are essential for myeloid differentiation, and that the CD11d promoter may be used as a model gene to identify transcription factors essential for myeloid cell differentiation.

Β2 (CD18) integrin-mediated leukocyte cell adhesion limit in various events essential for normal immune function. C011 a/CD18 (LFA-1), CD11 B / CD18 (MAC-1), and CD11c/CD18 (P150, 95): In spite of extensive research in this area, only three of this subfamily members are described in integrins. We have identified a DNA encoding the ads associate chain of fourth, the C018. Ad subunits, is connected to the CD11c and CD11b closely CD11a or more. This integrin, tissue foam cells found in a special aortic fatty streaks that occur in atherosclerotic lesions and such, is expressed at the level of moderate and subsets myeloid cell line of peripheral blood leukocytes, such as macrophages, It is larger cells than the compartment. I show a preferential recognition of ICAM-3 than ad/CD18 molecule ICAM-1.

The encoding can be found in the leukocyte integrin family α subunit late, CD11d is expressed primarily in bone marrow cells. We separate the genomic clone containing the CD11d, it indicates that this gene is a downstream-oriented 11461 bp in the same direction as the relatedCD11c gene. CD11d transcription begins 69-79 nucleotides upstream of the ATG codon. Transfection assay ofCD11d Luc reporter, area of ​​+74 to -173 is sufficient to white blood cell specific expression (HL60 and THP1), luciferase and B cells (IM9), T cells in the (Jurkat cells) bone marrow cells Build you made it clear that it is. The down-regulation of CD11d expression by phorbol esters is a bone marrow-specific transfection analysis shows that it has been provided by morecis element one or +74 region from -173. DNase I footprint analysis in the in vitro, SP3 bind and -40 ~ SP1 in the -63 clearly in the electrophoretic mobility shift assay. Deletion of the binding site of Sp is decreased significantly CD11d promoter activity. In the presence of phorbol esters leads to activation of the CD11d promoter, whereas downregulation of one of the factors of the antisense oligonucleotides, overexpression of SP3 also decreased CD11d promoter activity or Sp1 in THP1 cells. In contrast to the SP3 of the IM9 in regulatedCD11d promoter expression down Jurkat cells, overexpression. Genomic imprinting in vivo revealed that not the HL60 cells Sp to -63 to -40 region is not stimulated, it is bound to proteins in HL60 cells phorbol ester stimulation. In this site, both of phorbol ester stimulation and do not stimulate Jurkat cells and IM9 Unlike target. Taken together, these results indicate that the ofCD11d achieved by SP3 and SP1 down-regulation phorbol esters marrow specific.

Leukocyte integrin gene CD11d expressed on a subset of bone marrow line (bone marrow cells), especially in the red pulp macrophage foam macrophages and predominantely cells and spleen. Expression pattern is different from the specific integrin CD11a and white blood cells and CD11c-positive bone marrow-specific leukocyte integrin CD11b. CD11d functions are not defined in detail, its expression in the cells of these types has been suggested that it may play a role in atherosclerosis it. In order to understand how good this gene is regulated, CD38 + cells, peripheral blood monocytes and monocyte cell line CD11a and steady-state level of CD11d mRNA in differentiation of bone marrow CD34 was evaluated by RT-PCR and Northern blot , I was compared to that of CD11c with the CD11b. In contrast to the expression of the leukocyte integrin other, CD34 + CD38-cells, expression of CD11d will rise, and you will occur at the beginning of, then decreased. Expression of reproduction CD11d distinguishes macrophage foam cells in the peripheral blood mononuclear cells. Peripheral blood monocytes and acetylation and lipoproteins (of oxLDL) oxidized lipoprotein (AcLDL), failed to activate the differentiation of CD11d next monocytic cell line HL60. However, when oxLDL Noto AcLDL was present during differentiation, CD11d were further adjusted. This suggests that it is coordinated with the regulated expression of the development of foam cells and LDL receptor expression CD11d. -100 Directed mutagenesis revealed CD11d transcription factor binding sites necessary for expression of this gene in the -20 region of the promoter. Are occupied by CD34 block the differentiation of bone marrow colony + CD38-cells decoy oligonucleotide -100 to -20 region. This means essential CD11d that also for myeloid differentiation, and CD11d promoter, transcription factors of the one or more controls may be used as a model for the identification of gene transcription factor essential for differentiation of bone marrow cells I could.