Inhibition and stimulation of LFA-1 and Mac-1 functions by antibodies against murine CD18. Evidence that the LFA-1 binding sites for ICAM-1, -2, and -3 are distinct

Driessens, M. H. E.; Hulten, P. Van; Zuurbier, A.E.M.; Rivière, G. La; Roos, E.

doi:10.1002/jlb.60.6.758

Cited by 30 publications

(23 citation statements)

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“…injection of Chlamydia trachomatis (16). However, to confirm that the results with 2E6 were indeed due to functional inhibition of CD18, we used another anti-mouse CD18 mAb, GAME-46 (42). This was used in a recent study (38) to attenuate leukocyte adhesion in TNF-␣-stimulated venules of wild-type mice and confirms observations made in vessels of CD18 Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 75%

Differential Effects of CD18, CD29, and CD49 Integrin Subunit Inhibition on Neutrophil Migration in Pulmonary Inflammation

Ridger

Wagner

Wallace

et al. 2001

The Journal of Immunology

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Neutrophil migration to lung alveoli is a characteristic of lung diseases and is thought to occur primarily via capillaries rather than postcapillary venules. The role of adhesion molecules CD18 and CD29 on this migration in a mouse model of lung inflammation has been investigated. The number of neutrophils present in bronchoalveolar lavage fluid was determined 4 h after intratracheal instillation of LPS (0.1–1 μg) or murine recombinant KC (CXC chemokine, 0.03–0.3 μg). Both stimuli produced a dose-related increase in neutrophil accumulation. Intravenous anti-mouse CD18 mAb, 2E6 (0.5 mg/mouse), significantly (p < 0.001) attenuated LPS (0.3 μg)- but not KC (0.3 μg)-induced neutrophil accumulation. The anti-mouse CD29 mAb, HMβ1-1 (0.02 mg/mouse), significantly (p < 0.05) inhibited both LPS (0.3 μg)- and KC (0.3 μg)-induced neutrophil migration. A second mAb to CD18 (GAME-46) and both F(ab′)2 and Fab of HMβ1-1 produced similar results to those above, while coadministration of mAbs did not result in greater inhibition. Electron microscopy studies showed that CD29 was involved in the movement of neutrophils from the interstitium into alveoli. The effect of mAbs to CD49 (α integrin) subunits of CD29 was also examined. mAbs to CD49e and CD49f inhibited both responses, while anti-CD49b and CD49d significantly inhibited responses to KC only. These data suggest that CD29 plays a critical role in neutrophil migration in pulmonary inflammation and that CD49b and CD49d mediate CD18-independent neutrophil accumulation.

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Section: Discussionmentioning

confidence: 75%

Differential Effects of CD18, CD29, and CD49 Integrin Subunit Inhibition on Neutrophil Migration in Pulmonary Inflammation

Ridger

Wagner

Wallace

et al. 2001

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

“…It is of particular interest that transmigration of mouse hybridomas was also mediated through an LFA-1-dependent mechanism, despite the reported inability of mouse LFA-1 to ligate human ICAM-1 (41). Previous work has shown ligation of mouse LFA-1 by human ICAM-2 and -3, implying that these receptors contribute to antigen-specific T-cell migration (41). The recently discovered family of junctional adhesion molecules (14) that also interact with integrins may be involved in antigen-directed T-cell/EC interactions, and the relative importance of these different LFA-1 counter receptors will require further scrutiny.…”

Section: Discussionmentioning

confidence: 99%

Processing and Presentation of the Islet Autoantigen GAD by Vascular Endothelial Cells Promotes Transmigration of Autoreactive T-Cells

et al. 2003

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Type 1 diabetes is characterized by T-cell infiltration of the islets of Langerhans and abundant HLA class II molecule expression on islet endothelial cells (ECs).The specificity of infiltrating T-cells for islet autoantigens has been amply demonstrated in animal models, and is implicit in human diabetes, but the processes regulating endothelial transmigration of islet autoantigen-specific T-cells into islets are not known. We examined the ability of ECs expressing HLA class II molecules to process and present the islet autoantigen GAD65 and examined the effects of presentation on transmigration of GAD65-specific T-cells. Primary cultures of human vascular ECs expressing the DRB1*0401 (VEC1) and DRB1*0301 (VEC2) genotypes were established and de novo expression of HLA class II molecules induced with interferon-␥. Under these conditions, VEC1 efficiently processed and presented whole GAD65 to the HLA-DR4 -restricted murine T-cell hybridoma T33.1 that recognizes the 274-286 epitope of GAD65. Using a transwell system, we examined the effect of GAD65 presentation on migration of GAD65-specific T-cells across EC monolayers. Migration of T33.1 hybridoma cells and of the human T-cell clone, PM1#11 (recognizes GAD65 epitope 339-352 presented by HLA-DR3) across VEC1 and VEC2, respectively, were greatly enhanced in the presence of GAD65, commencing more rapidly and achieving a higher peak migration at 3 h. Migrated PM1#11 cells retained full proliferative capacity. These results support the hypothesis that presentation of autoantigens by islet endothelium in vivo could promote transmigration of circulating islet autoantigen-specific T-cells primed in regional lymph nodes against islet autoantigens. Diabetes 52:717-725, 2003

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“…Another difference is that ICAM-1 is present on the membrane as a dimer (39), whereas at least ICAM-2 appears to be a monomer (40). Finally, the fact that murine LFA-1 can bind human ICAM-2 and ICAM-3, but not ICAM-1, implies that the first two ligands might have structural features in common not shared with ICAM-1 (41). Taken together, the implication of these observations is that the interaction of LFA-1 with ICAM-1 has special features distinct from that interaction with ICAM-2 and ICAM-3.…”

Section: Discussionmentioning

confidence: 99%

A novel leukocyte adhesion deficiency caused by expressed but nonfunctional β2 integrins Mac-1 and LFA-1

Hogg¹,

Stewart²,

Scarth³

et al. 1999

J. Clin. Invest.

164

134

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The adhesive response of circulating leukocytes to inflammatory stimuli is now well documented (1, 2). After such signals, leukocytes adhere to the blood vasculature using selectin-mediated interactions, and this stage leads to activation of their integrins. The β2 or leukocyte integrins lymphocyte function-associated molecule (LFA)-1 (CD11a/CD18) has a major role in the firm adhesion of leukocytes to endothelium and in their migration across this barrier. In addition, LFA-1 cooperates with the T-cell receptor in antigen-stimulated T-cell priming (3) and, in general, participates in the formation of leukocyte-leukocyte contacts. Mac-1 (CD11b/CD18) is a major phagocytic receptor operating in association with the third β2 integrin, p150,95 (CD11c/CD18), and both recognize as ligands fibrinogen and the complement fragment iC3b (4, 5).Expression of integrins on the cell membrane is not a guarantee of their ability to function as adhesion receptors. Integrins must undergo conversion from inactive to active ligand-binding status, which occurs through a process of clustering and/or altered conformation (6, 7). The stimulus for this activation is initiated by the triggering of other membrane receptors, a route of signal transduction that has been termed "inside out" signaling. The integrins bind divalent cations such as Mg 2+ or Mn 2+ in order to function, and an alternative means of directly altering integrin activity is through extracellular exposure to these cations. It is thought that these latter procedures mimic the conformational changes brought about by integrin-activating signals generated intracellularly. Special anti-integrin monoclonal antibodies (MABs) can serve as reporters of this activation. For example, MAB 24 recognizes an epitope on high-affinity β2 integrin (7) and detects a conformational change in the form of interdomain movement involving the ligand binding I domain on the integrin α subunit (8).Valuable information about the functioning of the β2 integrins has come from study of the leukocyte adhesion deficiency (LAD)-1 syndrome. LAD-1 is an autosomal recessive disorder caused by mutation in the CD18 gene on chromosome 21 that leads to absent or aberrant biosynthesis of the β2 subunit of leukocyte integrins (9-11). This lesion is reflected in the absence or markedly diminished expression on the leukocyte cell surface of the β2 integrins, CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), and CD11c/CD18 (p150,95). The patient phenotype is variable but reflects the level of β2 integrins expressed. Patients with <1% expression suffer from life-threatening infections and require bone marrow transplantation for long-term survival (12). In patients with 1%-10% expression, defects in leukocyte mobility, adherence, and endocytosis lead to periodic periodontitis, skin infections, and retarded wound healing with dysplastic scarring. The heterozygotic relatives of the patients have ∼40%-60% normal levels of β2 inte- In the leukocyte adhesion deficiency (LAD)-1 syndrome, there is diminished expression of β2 (CD18) inte...

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Inhibition and stimulation of LFA-1 and Mac-1 functions by antibodies against murine CD18. Evidence that the LFA-1 binding sites for ICAM-1, -2, and -3 are distinct

Cited by 30 publications

References 0 publications

Differential Effects of CD18, CD29, and CD49 Integrin Subunit Inhibition on Neutrophil Migration in Pulmonary Inflammation

Differential Effects of CD18, CD29, and CD49 Integrin Subunit Inhibition on Neutrophil Migration in Pulmonary Inflammation

Processing and Presentation of the Islet Autoantigen GAD by Vascular Endothelial Cells Promotes Transmigration of Autoreactive T-Cells

A novel leukocyte adhesion deficiency caused by expressed but nonfunctional β2 integrins Mac-1 and LFA-1

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