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At least 991 records · Page 55Linked to original sources
PubMed1998

Ten-year follow-up study of allergen-specific immunoglobulin E and immunoglobulin G4, soluble interleukin-2 receptor, interleukin-4, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in serum of patients on immunotherapy for perennial allergic rhinitis.

Recent double-blind placebo-controlled trials for perennial allergic rhinitis have all clearly shown the efficacy of immunotherapy. Although several mechanisms for the clinical efficacy of immunotherapy have been proposed, the exact mechanisms related to the clinical effect still remain unclear. Since immunotherapy is a form of systemic treatment and its clinical benefit is likely to be, at least in part, a consequence of its systemic effects on different phases of immunological events, our study focused exclusively on several immunological parameters in serum. A total of 47 patients with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective study. Venous blood was collected for determination of specific immunoglobulin (Ig)E, specific IgG4, soluble interleukin-2 receptor (IL-2R), interleukin-4 (IL-4), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1), six times from 20 untreated patients and 27 patients on immunotherapy, at enrolment, and 1, 2, 3, 5, and 10 years after enrollment. No specific IgE, IgG4, soluble IL-2R, IL-4 and soluble ICAM-1 levels changed significantly for a span of 10 years in the untreated patients. By contrast, immunotherapy affected serum levels of specific IgE, specific IgG4, soluble IL-2R, IL-4 and soluble ICAM-1, but not of soluble VCAM-1. The rates of increase in specific IgG4 and the rates of decrease in soluble IL-2R were correlated with the rates of decrease in symptom scores during the first 3 years, but not 5 and 10 years after the course of immunotherapy. On the other hand, the rates of decrease in specific IgE, IL-4 and soluble ICAM-1 were significantly correlated with the rates of decrease in symptom scores at 5 and 10 years, but not during the first 3 years. Each immunological modulation by immunotherapy was likely to be involved in the working mechanism related to clinical efficacy at different phases of immunotherapy.

Adolescent↗
PubMed2003

Effects of the prostaglandin I2 analogue, beraprost sodium, on vascular cell adhesion molecule-1 expression in human vascular endothelial cells and circulating vascular cell adhesion molecule-1 level in patients with type 2 diabetes mellitus.

Beraprost sodium is an orally active prostaglandin (PG)I(2) analogue, which has antiplatelet and vasodilating properties. In this study, we investigated the effects of beraprost on the expression of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules involved in atherosclerosis, in cultured vascular endothelial cells. In addition, we examined the effects of beraprost on circulating VCAM-1 level and atherosclerosis progression in patients with type 2 diabetes mellitus. Beraprost significantly decreased tumor necrosis factor-alpha (TNF-alpha)-induced VCAM-1 expression in human vascular endothelial cells. Beraprost also repressed human monocytoid U937 cell adhesion to the vascular endothelial cells. Twenty-five patients with type 2 diabetes mellitus who had atherosclerotic change of carotid arteries were enrolled for an open prospective study: 11 patients received beraprost for 3 years, while the other 14 did not. The 3-year changes of circulating VCAM-1 level, as well as those of carotid arterial intima-media thickness (IMT) were significantly lower in the patients receiving the beraprost treatment than that in the patients without the treatment. Thus, beraprost had an ability to repress the expression of VCAM-1 in human vascular endothelial cells. In addition, beraprost lowered circulating VCAM-1 level and prevented the increase of carotid IMT in patients with type 2 diabetes mellitus. Considering that circulating VCAM-1 and IMT are predictive of future vascular events, beraprost may have a beneficial effect on progression of atherosclerosis in diabetic patients.

Carotid Arteries↗
PubMed1996

Homophilic adhesion mediated by the neural cell adhesion molecule involves multiple immunoglobulin domains.

The neural cell adhesion molecule (N-CAM) mediates homophilic binding between a variety of cell types including neurons, neurons and glia, and neurons and muscle cells. The mechanism by which N-CAM on one cell interacts with N-CAM on another, however, is unknown. Attempts to identify which of the five immunoglobulin-like domains (Ig I-V) and the two fibronectin type III repeats (FnIII 1-2) in the extracellular region of N-CAM are involved in this process have led to ambiguous results. We have generated soluble recombinant proteins corresponding to each of the individual immunoglobulin domains and the combined FnIII 1-2 and prepared polyclonal antibodies specific for each. The purified proteins and antibodies were used in aggregation experiments with fluorescent microspheres and chicken embryo brain cells to determine possible contributions of each domain to homophilic adhesion. The recombinant domains were tested for their ability to bind to purified native N-CAM, to bind to each other, and to inhibit the aggregation of N-CAM on microspheres and the aggregation of neuronal cells. Each of the immunoglobulin domains bound to N-CAM, and in solution all of the immunoglobulin domains inhibited the aggregation of N-CAM-coated microspheres. Soluble Ig II, Ig III, and Ig IV inhibited neuronal aggregation; antibodies against whole N-CAM, the Ig III domain, and the Ig I domain all strongly inhibited neuronal aggregation, as well as the aggregation of N-CAM-coated microspheres. Of all the domains, the third immunoglobulin domain alone demonstrated the ability to self-aggregate, whereas Ig I bound to Ig V and Ig II bound to Ig IV. The combined FnIII 1-2 exhibited a slight ability to self-aggregate but did not bind to any of the immunoglobulin-like domains. These results suggest that N-CAM-N-CAM binding involves all five immunoglobulin domains and prompt the hypothesis that in homophilic cell-cell binding mediated by N-CAM these domains may interact pairwise in an antiparallel orientation.

Animals↗
PubMed1995

The cytoplasmic domain of the Drosophila cell adhesion molecule neuroglian is not essential for its homophilic adhesive properties in S2 cells.

Drosophila neuroglian is a transmembrane glycoprotein that has strong structural and sequence homology to the vertebrate L1 gene family of cell adhesion molecules (Bieber, A.J., Snow, P.M., Hortsch, M., Patel, N.H., Jacobs, J.R., Traquina, Z.R., Schilling, J., and Goodman, C.S. (1989) Cell 59, 447-460. Two different neuroglian protein forms that are generated by a differential splicing process are expressed in a tissue-specific fashion by embryonic and larval cells (Hortsch, M., Bieber, A.J., Patel, N.H., and Goodman, C.S. (1990) Neuron 4, 697-709). The two neuroglial polypeptides differ only in their cytoplasmic domains. Both of these neuroglian species, when transfected into the expressed in Drosophila S2 cells, induce the calcium-independent, homophilic aggregation of transformed cells. A third artificial neuroglian protein form was constructed by substituting the neuroglian transmembrane segment and cytoplasmic domains with the glycosyl phosphatidylinositol attachment signal of the Drosophila fasciclin I protein. This cDNA construct generates a glycosyl phosphatidylinositol-anchored form of neuroglian, which retains the ability to induce homophilic cell aggregation when expressed in S2 cells, and was able to interact with both of the two naturally occurring neuroglian polypeptides. These results demonstrate that neuroglian mediates a calcium-independent, homophilic cell adhesion activity and that neither cytoplasmic neuroglian domains nor a direct interaction with cytoskeletal elements is essential for this property.

Amino Acid Sequence↗
PubMed2001

Ezrin interacts with focal adhesion kinase and induces its activation independently of cell-matrix adhesion.

Ezrin, a membrane-cytoskeleton linker, is required for cell morphogenesis, motility, and survival through molecular mechanisms that remain to be elucidated. Using the N-terminal domain of ezrin as a bait, we found that p125 focal adhesion kinase (FAK) interacts with ezrin. We show that the two proteins coimmunoprecipitate from cultured cell lysates. However, FAK does not interact with full-length ezrin in vitro, indicating that the FAK binding site on ezrin is cryptic. Mapping experiments showed that the entire N-terminal domain of FAK (amino acids 1-376) is required for optimal ezrin binding. While investigating the role of the ezrin-FAK interaction, we observed that, in suspended kidney-derived epithelial LLC-PK1 cells, overproduction of ezrin promoted phosphorylation of FAK Tyr-397, the major autophosphorylation site, creating a docking site for FAK signaling partners. Treatment of the cells with a Src family kinase inhibitor reduced the phosphorylation of Tyr-577 but not that of Tyr-397, indicating that ezrin-mediated FAK activation does not require the activity of Src kinases. Altogether, these observations indicate that ezrin is able to trigger FAK activation in signaling events that are not elicited by cell-matrix adhesion.

Animals↗
PubMed1992

Intercellular adhesion molecule 3, a third adhesion counter-receptor for lymphocyte function-associated molecule 1 on resting lymphocytes.

Recent studies suggest that some T and B lymphocyte cell lines bind to the integrin lymphocyte function-associated molecule 1 (LFA-1) chiefly through a pathway independent of its two known counter-receptors, intercellular adhesion molecules (ICAMs)-1 and -2. A monoclonal antibody (mAb) was raised that, in combination with blocking mAb to ICAM-1 and ICAM-2, can completely inhibit binding of these cell lines to purified LFA-1. This third ligand, designated ICAM-3 based on its functional relatedness to ICAM-1 and -2, is a highly glycosylated protein of 124,000 Mr. It is well expressed on all leukocytes and absent from endothelial cells. In assays of adhesion of resting lymphocytes to purified LFA-1, ICAM-3 is by far the most functionally important ICAM, implying an important role for ICAM-3 in the generation of immune responses.

Animals↗
PubMed1995

Intercellular adhesion molecule-1 dimerization and its consequences for adhesion mediated by lymphocyte function associated-1.

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a ligand for the integrins lymphocyte function associated-1 (LFA-1, CD11a/CD18) and complement receptor-3 (Mac-1, CD11b/CD18) making it an important participant in many immune and inflammatory processes. Modified recombinant soluble ICAM-1 formed dimers. This result indicated that the ectodomain of ICAM-1 contains homophilic interaction sites. Soluble ICAM-1 dimers bind to solid-phase purified LFA-1 with high avidity (dissociation constant [Kd] = 8 nM) in contrast to soluble ICAM-1 monomers whose binding was not measurable. Cell surface ICAM-1 was found to be dimeric based on two distinct criteria. First, a monoclonal antibody specific for monomeric soluble ICAM-1, CA7, binds normal ICAM-1 poorly at the cell surface; this antibody, however, binds strongly to two mutant forms of ICAM-1 when expressed at the cell surface, thus identifying elements required for dimer formation. Second, chemical cross-linking of cell surface ICAM-1 on transfected cells and tumor necrosis factor-activated endothelial cells results in conversion of a portion of ICAM-1 to a covalent dimer. Cell surface ICAM-1 dimers are more potent ligands for LFA-1-dependent adhesion than ICAM-1 monomers. While many extracellular matrix-associated ligands of integrins are multimeric, this is the first evidence of specific, functionally important homodimerization of a cell surface integrin ligand.

Animals↗
PubMed1991

Structural and functional studies of full-length vascular cell adhesion molecule-1: internal duplication and homology to several adhesion proteins.

Full-length vascular cell adhesion molecule-1 (VCAM-1) cDNA cloned by polymerase chain reaction (PCR) of poly(A)+RNA from interleukin-1 (IL-1)-activated human umbilical vein endothelial cells (HUVEC) contained an insert of 276 nucleotides after position 1,034 of the previously published sequence. Synthetic oligomer probes, specific for each of the two possible species of VCAM-1 mRNA, detected only the longer form of VCAM-1 by Northern analysis of activated endothelial cell mRNA. This full-length VCAM-1 contains two internally repeated domains of approximately 273 amino acids with a high degree of homology. This new sequence information reveals homologies with additional members of the immunoglobulin superfamily and improves ALIGN scores for previously cited adhesion proteins. Removal of the transmembrane domain and the carboxy-terminal end of the full-length VCAM-1 molecule allows the molecule to be secreted into the culture medium from cells transfected with an expression vector containing the corresponding VCAM-1 cDNA.

Amino Acid Sequence↗
PubMed2000

Differential modulation of cadherin-mediated cell-cell adhesion by platelet endothelial cell adhesion molecule-1 isoforms through activation of extracellular regulated kinases.

The role of platelet endothelial cell adhesion molecule-1 (PECAM-1) in endothelial cell-cell interactions and its contribution to cadherin-mediated cell adhesion are poorly understood. Such studies have been difficult because all known endothelial cells express PECAM-1. We have used Madin-Darby canine kidney (MDCK) cells as a model system in which to evaluate the role of PECAM-1 isoforms that differ in their cytoplasmic domains in cell-cell interactions. MDCK cells lack endogenous PECAM-1 but form cell-cell junctions similar to those of endothelial cells, in which PECAM-1 is concentrated. MDCK cells were transfected with two isoforms of murine PECAM-1, Delta15 and Delta14&15, the predominant isoforms expressed in vivo. Expression of the Delta15 isoform resulted in apparent dedifferentiation of MDCK cells concomitant with the loss of adherens junctions, down-regulation of E-cadherin, alpha- and beta-catenin expression, and sustained activation of extracellular regulated kinases. The Delta15 isoform was not concentrated at cell-cell contacts. In contrast, the Delta14&15 isoform localized to sites of cell-cell contact and had no effect on MDCK cell morphology, cadherin/catenin expression, or extracellular regulated kinase activity. Thus, the presence of exon 14 in the cytoplasmic domain of PECAM-1 has dramatic effects on the ability of cells to maintain adherens junctions and an epithelial phenotype. Therefore, changes in the expression of exon 14 containing PECAM-1 isoforms, which we have observed during development, may have profound functional consequences.

Animals↗
PubMed2001

An approach to enhance the interface adhesion between an orthodontic plastic bracket and adhesive.

For the purpose of improving the degree of success of plastic bracket bonding, based on the analysis of the chemical components of plastic brackets, a systematic method for the treatment of the adhesive surface of plastic brackets was introduced in this study. After sandblasting the adhesive surfaces of two commercially available plastic brackets (Spirit and Clear Bracket), a favourable surface treatment was obtained with the application of a silane coupling agent, gamma-methacryloxy propyl trimethoxy silane. The findings showed that (i) the fillers added to the plastic brackets were glass fillers with Si-OH groups distributed on their surfaces; (ii) sandblasting of the bracket surface resulted in exposure of the glass fillers; (iii) combined with sandblasting, silane coupling treatment significantly increased the bond strength (P < 0.05), which was adequate to withstand the forces generated during orthodontic therapy; and (iv) treatment with sandblasting and silane coupling 24 hours before direct bonding did not cause a significant reduction in bond strength. It is concluded that sandblasting and silane coupling treatment offers the benefit of increasing the in vitro bond strength of plastic brackets for orthodontic application.

Adhesiveness↗
PubMed2001

Vascular endothelial growth factor, platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 in the follicular fluid of patients undergoing IVF.

BACKGROUND: The aim of our study was to measure concentrations of vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1) CD31 and vascular cell adhesion molecules (VCAM-1) in the follicular fluid of women treated with assisted reproduction technology to determine whether these proteins might be outcome markers. METHODS: Follicular fluid was collected from 75 patients < or =40 years undergoing oocyte retrieval procedures at our tertiary hospital during 1997 and 1998: 50 with tubal disease, 12 with endometriosis, and 13 whose partners had been diagnosed with severe oligoasthenoteratozoospermia. This retrospective analysis considered age and information about treatment and outcome for all these women who had undergone fewer than three assisted reproduction attempts. RESULTS: Nineteen women became pregnant (defined by human chorionic gonadotrophin concentrations and embryonic cardiac activity 1 month after follicular aspiration); 56 did not. Women did not differ significantly in their follicular fluid concentrations of VEGF, sCD31 and VCAM-1 according to cause of infertility, or assisted reproduction outcome, or age. Follicular fluid concentrations of VEGF were significantly correlated with the number of gonadotrophin ampoules administered (P < 0.012), and follicular fluid concentrations of sVCAM-1 with the fertilization rate (P < 0.01). Follicular fluid concentrations of VEGF and sVCAM-1 were also correlated (P < 0.007). CONCLUSIONS: Our results do not suggest that VEGF, CD31, or sVCAM-1 in follicular fluid predict assisted reproduction outcome, especially among patients < or =40 years old. The correlation of a high fertilization rate and sVCAM-1 in follicular fluid suggests that sVCAM-1 might be a marker of fertilization.

Abortion, Spontaneous↗
PubMed1992

Engineering of artificial cell adhesion proteins by grafting the Arg-Gly-Asp cell adhesive signal to a calpastatin segment.

A new artificial cell adhesive protein was engineered by grafting the Arg-Gly-Asp (RGD) sequence, the minimal recognition signal of fibronectin for interaction with integrins, to a calpastatin segment by in vitro mutagenesis. The mutagenized protein showed cell adhesive activity in addition to calpain inhibitory activity. The RGD signal grafted to the calpastatin segment was recognized by the vitronectin receptor but not by the fibronectin receptor.

Amino Acid Sequence↗
PubMed2003

Clinical effects of inhibiting leukocyte adhesion with monoclonal antibody to intercellular adhesion molecule-1 (enlimomab) in the treatment of partial-thickness burn injury.

BACKGROUND: A randomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial was performed to determine whether inhibition of leukocyte adherence by administration of monoclonal antibody directed against intercellular adhesion molecule-1 would improve burn wound healing. METHODS: One hundred ten patients with burn injury ranging from 10% to 30% total body surface area were enrolled. Fifty-six patients received placebo (saline) and 54 patients received murine monoclonal antibody to the human intercellular adhesion molecule-1 (enlimomab). Treatment was initiated within 6 hours of injury. Patients had three distinct partial-thickness wound sites assessed. Laser Doppler flowmetry was used to stratify wounds on the day of injury. Wounds were assessed for healing status on day 21 postburn and categorized as healed, nonhealed, or grafted. RESULTS: Patients treated with enlimomab had a significantly increased percentage of wounds that healed spontaneously in less than 21 days overall and when stratified by burn wound laser Doppler blood flow readings for those wounds at greatest risk for nonhealing. CONCLUSION: These results support the concept that leukocyte adherence is involved in the pathogenesis of burn wound necrosis and suggest a therapeutic mechanism for modulating the inflammatory response after the burn injury that may improve wound healing.

Adult↗
PubMed1990

Adhesion molecules on the plasma membrane of epidermal cells. II. The intercellular adhesion molecule-1 is constitutively present on the cell surface of human resting Langerhans cells.

The intercellular adhesion molecule-1 (ICAM-1), which is a member of the immunoglobulin superfamily, is expressed on many cell types, including a variety of cells showing accessory/antigen-presenting capacities and belonging to the monocyte/macrophage or dendritic lineages. Here it is shown that human freshly isolated Langerhans cells (LC) constitutively express ICAM-1, as expected. It seems likely that the amounts of ICAM-1 moieties expressed on the plasma membrane of resting LC are only limited, since they virtually escaped detection by conventional immunofluorescence procedures on epidermal sheets. However, all the observed Birbeck granule-bearing LC showed their clear, although relatively weak, ICAM-1 positivity when more sensitive techniques were employed, such as colloidal gold-immunoelectronmicroscopy using gold particles 15nm in size and, to an even higher extent, using gold particles 5 nm in size. Because ICAM-1 is a ligand for the adhesive molecule LFA-1, which is expressed on the surface of leukocytes and, especially, lymphocytes, the ICAM-1 (LC)/LFA-1 (T-lymphocytes) interactions might, enabling these cells to adhere together, deliver activation signals to T cells, thus constituting the initial event in the generation of a cutaneous immune response.

Cell Adhesion Molecules↗
PubMed2003

Small molecule antagonists of complement receptor type 3 block adhesion and adhesion-dependent oxidative burst in human polymorphonuclear leukocytes.

The leukocyte integrin complement receptor type 3 (CR3, Mac-1, CD11b/CD18) is the predominant beta(2) integrin receptor of polymorphonuclear leukocytes (PMNs). This cell surface receptor plays a central role in innate immunity against pathogens as well as being a major cellular effector of inflammation and tissue injury. Two small molecules, compounds 1 and 2, have been identified, that interact with CR3 and prevent CR3 from binding to its natural ligand, C3bi. Compounds 1 and 2 have IC(50) values of 0.14 and 0.33 microM, respectively, for the inhibition of binding of monomeric C3bi-alkaline phosphatase to immobilized CR3. Both compounds also inhibit binding of CR3 to biotinylated sheep red blood cells opsonized with C3bi, with IC(50) values in the micromolar range. Inhibition of ligand binding by the compounds is not easily reversed and requires light, suggesting the formation of a covalent adduct through photoactivation. Compounds 1 and 2 also inhibit adhesion of human PMNs to fibrinogen in response to tumor necrosis factor (TNF) or PMA, with IC(50) values of 2.5 to >10 microM. They block the adhesion-dependent production of H(2)O(2) stimulated by TNF or phorbol 12-myristate 13-acetate (PMA) with IC(50) values of 0.2 to 0.8 microM and 1 to 3 microM, respectively. Limited structure-activity relationship studies based on compound 2 indicate the importance of the two benzothiazole rings, an ethyl side chain, and the length of the carbon chain linking the rings. Further modification of these groups may help in making compounds appropriate for in vivo studies.

Benzothiazoles↗
PubMed1996

CD36 and intercellular adhesion molecule 1 mediate adhesion of developing Plasmodium falciparum gametocytes.

Plasmodium falciparum trophozoite-infected erythrocytes adhere to the amelanotic melanoma C32 cell line in vitro. Here we demonstrate for the first time that immature gametocyte-infected erythrocytes also adhere to C32 cells, albeit at lower levels than trophozoites. However, anti-CD36 and anti-intercellular adhesion molecule 1 antibodies inhibit asexual and gametocyte adhesion by comparable percentages, suggesting a common dependency for binding to these cellular receptors.

Adhesiveness↗
PubMed2002

Focal adhesions require catalytic activity of Src family kinases to mediate integrin-matrix adhesion.

Members of the Src family of tyrosine kinases function to phosphorylate focal adhesion (FA) proteins. To explore the overlapping functions of Src kinases, we have targeted Csk, a negative regulator of the Src family, to FA structures. Expression of FA-targeted Csk (FA-Csk) effectively reduced the active form (nonphosphorylated at the C-terminal regulatory tyrosine) of Src members in the cell. We found that fibroblasts expressing FA-Csk lost integrin-mediated adhesion. Activated Src (SrcY529F) as well as activation of putative Src signaling mediators (Fak, Cas, Crk/CrkL, C3G, and Rap1) blocked the effect of FA-Csk in a manner dependent on Rap1. SrcY529F also inhibited activated Ras-induced cell detachment but failed to rescue detachment caused by an activated mutant of Raf1 (Raf-BXB) that Rap1 cannot inhibit. Although normal spreading onto fibronectin was restored by the beta(1) integrin affinity-activating antibody TS2/16 in cells expressing FA-Csk or Raf-BXB, FAs were lost in these cells. On the other hand, Rap1 activation could restore FAs in cells expressing FA-Csk. Activation of the executioner caspase, caspase 3, is essential for many forms of apoptosis. While a caspase 3 inhibitor (Z-DEVD-FMK) inhibited cell detachment triggered by activation of caspase 8, this inhibitor had no effect on cell detachment caused by FA-Csk. Likewise, overexpression of an activated Akt made cells resistant to the effect of caspase 8 activation, but not to the effect of FA-Csk. It is therefore likely that the primary cause of cell rounding and detachment induced by FA-Csk involves dysfunction of FAs rather than caspase-mediated apoptosis that may result from possible loss of survival signals mediated by Src family kinases. We suggest that endogenous Src family kinases are essential for FAs through activation of Rap1 in fibroblasts.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Effects of different mediators or cytokines and monoclonal antibodies to adhesion molecules on leukocyte adhesion in rat mesenteric venules.

Leukocyte adhesion (LA) to the endothelium of postcapillary venules is considered to be an important step in the inflammatory response. The recruitment of blood leukocytes into sites of inflammation involves a well-coordinated and dynamic sequence of events in which several cellular adhesion molecules (CAMs) and chemotactic cytokines play an active role. The aim of the present study was to elucidate receptor-mediated interaction in mesenteric venules of leukocyte rolling/adhesion and plasma leakage. We applied intravital microscopic techniques, with the help of an analogous video image processing system, to measure changes in the microvascular integrity. Rat monoclonal antibodies (MoAb) to different CAMs were administered before inflammatory stimuli were applied. Topical application of different doses of either lipo-polysaccharide (LPS), fMet-Leu-Phe, zymosan, complement C5a, Tnf-alpha, interleukin-1beta (IL-1beta), IL2 or IL-6 resulted in a dose-dependent increase in LA. The injection of a MoAb (1 mg/kg), 15 min prior to the LPS challenge, resulted in (1) total inhibition of LA, when MoAb to rat L-section, LFA1-beta and VLA-4 were used, (2) a moderate effect with LFA-1beta and Mac-1 MoAb, and (3) only a weak influence on LA by the MoAb to rat ICAM-1 (1 mg/kg). No effects were seen with IgG1 control MoAb. LA in acute models of inflammation can be regarded as a consequence of time-dependent differential effects of CAMs, as observed through the application of different MoAb.

Animals↗