Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The leukocyte integrin complement receptor type III (CR3, CD11b/CD18) binds the C3 cleavage product iC3b. Many other integrins bind their ligands via an Arg-Gly-Asp (RGD) triplet. Both the RGD-containing C3 peptide 1390TRYRGDQDATMS1401 (pro-C3 numbering) and the RGD-like fibrinogen peptide GGAKQAGDV, which binds to the platelet integrin glycoprotein IIb-IIIa, were shown to inhibit the iC3b-CR3 interaction, suggesting that this binding is also RGD-mediated (Wright, S.D., Weitz, J.I., Huang, A. J., Levin, S.M., Silverstein, S.C., and Loike, J.D. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7734-7738). However, unlike other integrin-ligand interactions, that of CR3 and iC3b is unaffected by the hexapeptide GRGDSP, and substitutions in the RGD triplet of C3 from other species appear to be tolerated. It was, therefore, proposed (Grossberger, D., Marcuz, A., du Pasquier, L., and Lambris, J.D. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 1323-1327) that the highly conserved DATMS portion of the inhibitory C3 peptide may have been responsible for its binding. To address these inconsistencies and directly assess the role of the 1390-1401 segment within the complete iC3b molecule in mediating binding to CR3, a human C3 cDNA was altered by site-directed mutagenesis and the expressed recombinant proteins were examined in a CR3-specific assay. Replacement of RGD by AAA did not abolish rosetting of the corresponding iC3b-coated erythrocytes to human CR3-bearing leukocytes. In addition, mutant iC3b molecules in which the positively charged R1391 (corresponding to K in the fibrinogen peptide) and the highly conserved 1397DATMS sequence were replaced by Q and NAAMA respectively, were still bound by CR3. We conclude that the iC3b-CR3 interaction is not mediated by the RGD triplet or its neighboring residues.
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PMID:Mutagenesis of the Arg-Gly-Asp triplet in human complement component C3 does not abolish binding of iC3b to the leukocyte integrin complement receptor type III (CR3, CD11b/CD18). 173 Jun 24

The integrin alpha L beta 2 (leukocyte function-associated molecule 1, CD11a/CD18) mediates activation-dependent adhesion of leukocytes. The cytoplasmic domains of alpha L beta 2 have been demonstrated to modulate adhesiveness of alpha L beta 2. Affinity changes of alpha L beta 2 for its ligand or postreceptor events can be responsible for this modulation of adhesiveness. To investigate the possible role of the alpha L beta 2 cytoplasmic domains in postreceptor events we constructed cDNA encoding chimeric proteins with intracellular alpha L beta 2 domains, which are responsible for alpha L beta 2 specific intracellular interactions, and extracellular alpha IIIb beta 3 (GP IIb/IIIa) domains, which allow the assessment of the receptor affinity state. The cDNA was stably transfected in Chinese hamster ovary cells and chimeric heterodimer formation proven by immunoprecipitations and flow cytometry. The chimeric receptors mediate adhesion to immobilized fibrinogen, and this adhesion is increased by phorbol myristate acetate and abolished by cytochalasin D. However, neither treatment affects the affinity state of the chimeric receptor, suggesting involvement of the cytoskeleton in the regulation of alpha L beta 2 mediated cell adhesion. To exclude the possibility of postoccupancy affinity changes of the chimeric receptors, we locked the receptors into a high affinity state by creating a deletion variant. The region deleted (VGFFK) is highly conserved in integrin alpha subunit cytoplasmic domains. Cotransfection of this deletion variant with a beta subunit truncation (beta 3 delta 724) and a triple mutation at 758-760 (TTT to AAA) of beta 2 abolishes adhesion without changing the affinity state. A single mutation (TTT to TAT) reduces adhesion by half without affinity change. Scanning electron microscopy reveals impaired spreading of these truncated/mutated chimeras. Immunofluorescence microscopy demonstrates a correlation between impaired adhesion and a decrease in the ability to form focal adhesions and to organize the cytoskeleton into stress fibers. These results describe the integrin/cytoskeleton interaction, the organization of the cytoskeleton, and cell spreading as postreceptor events modulating alpha L beta 2 cytoplasmic domain mediated cell adhesion. Furthermore, we demonstrate that the cytoplasmic domain of the beta 2 subunit, and within it the TTT region, are required for these postreceptor events. Additionally, we present a new approach, using deletion variants to lock integrins in a high affinity state without interfering with the investigated integrin/cytoskeleton interaction. This approach may be generally useful to investigate the role of postreceptor events in integrin-mediated cell adhesion and migration.
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PMID:Modulation of cell adhesion by changes in alpha L beta 2 (LFA-1, CD11a/CD18) cytoplasmic domain/cytoskeleton interaction. 780 11

To investigate whether activated leukocytes are present in salvaged blood, we measured complete blood counts and quantified the surface expression of the leukocyte adhesion receptors CD11b and CD18 in salvaged blood and arterial blood from six male patients undergoing elective abdominal aortic aneurysm repair. Salvaged blood contained 5,450 +/- 1010 leukocytes/microL and 7600 +/- 6200 platelets/microL and had a hematocrit of 50.6 +/- 3.7%. CD 11b expression was 3.3 +/- 0.5 fold higher on neutrophils and 3.8 +/- 1.0 fold higher on monocytes from salvaged blood compared with arterial blood (P < 0.05 for both). CD18 expression was increased 3.2 +/- 0.2 fold on neutrophils and 2.5 +/- 0.4 fold on lymphocytes (P < 0.05) in salvaged compared to arterial blood (P < .05). Monocyte expression of CD18 was increased 4.50 +/- 1.1 fold in salvaged blood, but this difference was not statistically significant. We conclude that a substantial number of activated leukocytes are present in salvaged blood. Because activated leukocytes could potentially be detrimental to the recipient, our findings raise theoretical concerns about the use of salvaged blood and emphasize the need for further refinement of the procedure.
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PMID:Leukocyte CD11b and CD18 expression are increased in blood salvaged for autotransfusion. 794 46

The role of CD18 antibody (anti-CD18) in remote and local injury in a model of ruptured abdominal aortic aneurysm repair was investigated. Rats were divided into sham, shock, clamp, and shock + clamp groups. Shock + clamp animals received anti-CD18 or a control monoclonal antibody. One hour of hemorrhagic shock was followed by 45 min of supramesenteric aortic clamping. Intestinal and pulmonary permeability to (125)I-labeled albumin was determined. Myeloperoxidase (MPO) activity, F(2)-isoprostane levels, and transaminases were also measured. Only shock + clamp resulted in statistically significant increases in pulmonary and intestinal permeability, which were associated with significant increases in MPO activity and F(2)-isoprostane levels. Treatment with anti-CD18 significantly decreased intestinal and pulmonary permeability in shock + clamp animals. These reductions were associated with significantly reduced intestinal and hepatic MPO activity and pulmonary F(2)-isoprostane levels and reduced alanine and aspartate aminotransferase levels; however, anti-CD18 had no effect on intestinal or hepatic F(2)-isoprostane levels or on pulmonary MPO activity. These results suggest CD18-dependent and -independent mechanisms of local and remote organ injury in this model of ruptured abdominal aortic aneurysm.
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PMID:A CD18 monoclonal antibody reduces multiple organ injury in a model of ruptured abdominal aortic aneurysm. 1040 95

Ischemia and reperfusion in myocardial infarction and stroke are associated with upregulation of leukocyte adhesion molecules, which contributes to tissue injury by facilitating leukocyte adhesion and infiltration in the affected tissues. Surgical repair of the abdominal aortic aneurysm involves clamping and declamping of the aorta, which necessarily results in ischemia and reperfusion of the lower half of the body. Given the large volume of the affected tissues and unimpeded venous return during reperfusion, we hypothesized that the procedure may result in upregulation of leukocyte integrins in the systemic circulation. To test this hypothesis, we studied neutrophil and monocyte surface densities of CD11b and CD18 in patients undergoing elective infrarenal abdominal aortic aneurysm repair. Serial blood samples were collected from the radial artery and femoral vein during the operation and leukocyte CD11b and CD18 surface densities were quantified by flow cytometry. Following reperfusion, CD11b expression in neutrophils and monocytes increased significantly in femoral venous and arterial blood. The mean time to peak expression of CD11 b in neutrophils and monocytes during reperfusion was 34.4 and 31.4 minutes in venous and 38.5 and 36.4 minutes in arterial blood, respectively. Similar rises in CD18 expression on neutrophils and monocytes were observed in venous and arterial blood. The mean time to peak expression of CD18 in neutrophils and monocytes during reperfusion was 34.0 and 40.0 minutes in venous and 47.5 and 50.0 minutes in arterial blood, respectively.
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PMID:Systemic upregulation of leukocyte integrins in response to lower body ischemia-reperfusion during abdominal aortic aneurysm repair. 1571 80