Increased expression of intercellular adhesion molecule 1 (ICAM1), a protein known to contribute to inflammatory responses, has been detected in the brain tissue of patients with Alzheimer's disease (AD) and animals modelled to mimic AD or Parkinson's disease (PD). ICAM1 may, thus, be implicated in the pathogenesis of these disorders. Our purpose was to investigate whether genetic variants of the ICAM1 gene have a role in causing susceptibility to AD and/or PD. We genotyped the E469K polymorphism of ICAM1 in 196 AD, 52 PD and 202 control patients of Finnish origin. The distributions of the genotype and allele frequencies of the polymorphism did not differ significantly between the AD, PD or the control patients. We therefore conclude that the E469K polymorphism of ICAM1 is not a risk factor for AD or PD.
BACKGROUND: With the increasing need for organ transplantation and the use of "marginal" organs, novel approaches are sought to increase the efficiency and survival of transplanted tissue. We tested the idea that treatment with the anti-inflammatory peptide, alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous hormone that does not cause marked immunosuppression but does reduce reperfusion injury, may protect allografts and prolong their survival. METHODS: Donor cardiac grafts (Brown Norway) were transplanted heterotopically into the abdomen of recipient (Lewis) rats. Treatments consisted of intraperitoneal injections of Nle DPhe -alpha-MSH (NDP-alpha-MSH) or saline from the time of transplantation until sacrifice or spontaneous rejection. Allografts were removed on day 1, day 4, or at the time of rejection and examined for histopathology and expression of molecules prominent in reperfusion injury, transplant rejection, and apoptosis. RESULTS: NDP-alpha-MSH treatment caused a significant increase in allograft survival and a marked decrease in leukocyte infiltration. Expression of molecules such as endothelin 1, chemokines, and adhesion molecules, which are involved in allograft rejection, was significantly inhibited in NDP-alpha-MSH-treated rats. CONCLUSIONS: The results indicate that protection of the allograft from early injury with alpha-MSH can postpone rejection. Addition of this early protection with the peptide to usual treatment with immunosuppressive agents may, therefore, improve success of organ transplants.
Mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) has been implicated in the aberrant homing of intestinal lymphocytes to the liver in primary sclerosing cholangitis (PSC). Intercellular adhesion molecule-1 (ICAM-1) has also been implicated in the pathogenesis of PSC and the E/E genotype of the K469E polymorphism has been reported to be associated with PSC susceptibility. The aims of this study were to determine if MAdCAM-1 polymorphisms or the K469E polymorphism of ICAM-1 are associated with PSC in Scandinavia.
Seven single nucleotide polymorphisms (SNPs) in MAdCAM-1 and the G421R and K469E ICAM-1 SNPs were genotyped in 365 PSC patients from Norway and Sweden. 327 Norwegian ulcerative colitis (UC) patients and 368 Norwegian bone marrow donors served as controls.
No significant association with PSC was found for any of the MAdCAM-1 or ICAM-1 SNPs. Allele frequencies for these polymorphisms were not significantly different between PSC patients with UC, UC patients and healthy controls.
Polymorphisms in MAdCAM-1 are not likely to significantly affect PSC susceptibility. In addition, the E/E genotype of the K469E in ICAM-1 does not influence PSC susceptibility in Scandinavia.
Airway inflammation is involved in the pathogenesis of bronchial asthma. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen-1 alpha (LFA-1 alpha) and has been shown to be required for leukocyte migration into inflamed area. The purpose of this report was to investigate the role of ICAM-1/LFA-1 alpha pathway in a rat model of extrinsic asthma using monoclonal antibodies (mAbs). We chose to study ovalbumin (OA)-sensitized Brown-Norway rats, an animal model in which there is a high prevalence of both early (ER) and late responses (LR) after antigen challenge. We measured tracheal and alveolar pressure using alveolar capsules in open-chested, mechanically ventilated animals to calculate resistance of lung (RL), tissue (Rti), and airway (Raw). In the OA group, both ER (RL, Rti, Raw = 263 +/- 16, 235 +/- 10, 309 +/- 38% baseline) and LR (RL, Rti, Raw = 265 +/- 26, 238 +/- 13, 316 +/- 55% baseline) were observed. The administration of mAbs to ICAM-1 and LFA-1 alpha significantly attenuated the ER (RL, Rti, Raw = 146 +/- 9, 141 +/- 11, 156 +/- 8% baseline) and LR (RL, Rti, Raw = 128 +/- 8, 124 +/- 5, 137 +/- 1% baseline), indicating that both airway and lung tissues were involved in this mechanism. The current observations suggest that ICAM-1/LFA-1 alpha pathway is involved in both the early and late responses in a rat model of allergic asthma. The antagonism of ICAM-1 and LFA-1 alpha may provide a potential therapeutic approach to the early and late responses of bronchial asthma.
Low-dose methotrexate (MTX) is an established and highly effective treatment for severe psoriasis and rheumatoid arthritis; however, its mechanism of action remains unclear. We investigated the effects of low-dose MTX on antigen-stimulated peripheral blood mononuclear cells and explored through which cellular pathways these effects are mediated. We show that MTX caused a dose-dependent suppression of T cell activation and adhesion molecule expression, and this was not due to lymphocyte apoptosis. The suppression of intercellular adhesion molecule (ICAM)-1 was adenosine and folate-dependent, while MTX suppression of the skin-homing cutaneous lymphocyte-associated antigen (CLA) was adenosine-independent. The effect of MTX on CLA, but not ICAM-1, required the constant presence of MTX in cultures. Thus, the suppression of T cell activation and T cell adhesion molecule expression, rather than apoptosis, mediated in part by adenosine or polyglutamated MTX or both, are important mechanisms in the anti-inflammatory action of MTX.
The objective of the present study was to investigate if there was a difference in baseline serum concentrations of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) between groups with and without cardiovascular events during a mean follow-up of 6.6 years in a group of initially healthy 58-year-old men. A further aim was to examine if high serum concentrations of ICAM-1 and VCAM-1 were associated with carotid and femoral artery plaque occurrence, separately. Men with cardiovascular events during follow-up had higher median serum ICAM-I and VCAM-I than those without events (P
The aims were to study biomarkers of systemic inflammation, platelet/endothelial activation and thrombosis in tunnel construction workers (TCW).
Biomarkers and blood fatty acids were measured in blood of 90 TCW and 50 referents before (baseline) and towards the end (follow-up) of a 12 days work period. They had been absent from work for 9 days at baseline. Air samples were collected by personal sampling.
Personal thoracic air samples showed geometric mean (GM) particulate matter and a-quartz concentrations of 604 and 74 µg/m(3), respectively. The arithmetic mean (AM) concentration of elemental carbon was 51 µg/m(3). The GM (and 95% confidence interval) concentration of the pro-inflammatory cytokine TNF-a decreased from 2.2 (2.0-2.4) at baseline to 2.0 pg/mL (1.8-2.2) (p?=?0.02) at follow-up among the TCW. Also the platelet activation biomarkers P-selectin and CD40L decreased significantly [25.4 (24.1-26.6) to 24.4 (22.9-26.0)] ng/mL, p?=?0.04 and 125 (114-137) to 105 (96-115) pg/mL, p?
Cites: Am J Respir Crit Care Med. 2007 Aug 15;176(4):395-40017446340
The association between exposure during handling of sewage and compost and the serum concentration of inflammatory biomarkers was studied.
A total of 44 workers exposed to sewage dust, 47 workers exposed to compost dust and 38 referents from the administrative staff participated. Microbial aerosols were collected by personal inhalable samplers. The concentrations of bacterial cells, spores from fungi and bacteria (actinomycetes) and endotoxins were determined by fluorescence and scanning electron microscopy and the Limulus assay. Fibrinogen, D-dimer, ICAM-1, VCAM-1 and IL-6 were determined by ELISA and C-reactive protein (CRP) by HS-MicroCRP assay in blood samples collected post-shift.
The exposure to dust ranged from 0.02 to 11 mg/m(3), endotoxins from 1 to 3160 EU/m(3) and bacteria from 0 to 209 × 10(6) cells/m(3). Fungal (0-41 × 10(6) spores/m(3)) and actinomycetes spores (0-590 × 10(6) actinomycetes spores/m(3)) were observed only at compost plants. The exposed workers had significantly higher fibrinogen (arithmetic mean 3.3 mg/ml) and CRP (geometric mean 1.5 mg/L) compared to the referents (2.8 and 1.0 mg/L, respectively). The serum concentration of CRP was negatively associated with forced expiratory volume in one second (FEV1) in % of predicted. Exposure to inhalable dust and bacteria was positively associated with the serum concentration of ICAM-1.
This study suggests that exposure to bacteria and dust when handling sewage and compost may initiate an inflammation shown by an increase in serum concentration of ICAM-1. The higher concentrations of fibrinogen and CRP in exposed workers compared to the referents may reflect a low-grade systemic inflammation.
The content of soluble molecules of intercellular adhesion-1 (sICAM-1) in 60 patients with an acute thrombophlebitis (TP) of the lower extremities subcutaneous veins was studied preoperatively and 7 days after the operation using method of a solid phase immunoenzymatic analysis (IEA). The sICAM-1 level before treatment in men was increased at average by 75.8% (P
We investigated the potential role of intercellular-adhesion molecule-1 (ICAM-1) in allergen-induced bronchial hyperresponsiveness (BHR) and inflammation in sensitised Brown-Norway rats. Rats were sensitised with ovalbumin (OA) intraperitoneally and 21 days later they were either exposed to 0.9% NaCl or 1% OA aerosol for 15 min. Rats exposed to OA aerosol were pretreated either with ICAM-1 antibody (3 mg/kg i.p. and i.v., 45 min prior to OA exposure) or with the diluent for the antibody. Eighteen to twenty-four hours after OA or 0.9% NaCl exposure, rats were anaesthetised, tracheostomised and mechanically ventilated, and airway responsiveness to acetylcholine (ACh) aerosol was measured as the provocative concentration of ACh needed to increase pulmorary resistance by 100% (PC100). Mean -log PC100 was increased in rats exposed to OA but pretreated with diluent (2.75 +/- 0.06) compared to rats treated with ICAM-1 antibody (2.51 +/- 0.08;