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T cells are central to the pathogenesis of lupus nephritis (LN), a common complication of systemic lupus erythematosus (SLE). CD6 and its ligand, activated leukocyte cell adhesion molecule (ALCAM), are involved in T cell activation and trafficking. Previously, we showed that soluble ALCAM is increased in urine (uALCAM) of patients with LN, suggesting that this pathway contributes to disease. To investigate, uALCAM was examined in 1038 patients with SLE and LN from 5 ethnically diverse cohorts; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of SLE and acute glomerulonephritis. Extended cohort analysis offered resounding validation of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells whereas CD6 expression was exclusive to T cells, with elevated numbers of [CD6.sup.+] and [ALCAM.sup.+] cells in patients with LN. CD6 blockade in models of spontaneous lupus and immune-complex glomerulonephritis revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data demonstrate the contribution of the CD6/ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target., Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that predominantly affects women in the reproductive age range. Approximately 50% of patients with SLE experience lupus nephritis (LN), [...]

Congenital tufting enteropathy (CTE) is a severe autosomal recessive human diarrheal disorder with characteristic intestinal epithelial dysplasia. CTE can be caused by mutations in genes encoding EpCAM, a putative adhesion molecule, and HAI-2, a cell surface protease inhibitor. A similar phenotype occurs in mice whose intestinal epithelial cells (IECs) fail to express the tight junction-associated protein claudin-7. EpCAM stabilizes claudin-7 in IECs, and HAI-2 regulates the cell surface serine protease matriptase, a known modifier of intestinal epithelial physiology. Therefore, we hypothesized that HAI-2, matriptase, EpCAM, and claudin-7 were functionally linked. Herein we have demonstrated that active matriptase cleaves EpCAM after Arg80 and that loss of HAI-2 in IECs led to unrestrained matriptase activity and efficient cleavage of EpCAM. Cleavage of EpCAM decreased its ability to associate with claudin-7 and targeted it for internalization and lysosomal degradation in conjunction with claudin-7. CTE-associated HAI-2 mutant proteins exhibited reduced ability to inhibit matriptase and also failed to efficiently stabilize claudin-7 in IECs. These results identify EpCAM as a substrate of matriptase and link HAI-2, matriptase, EpCAM, and claudin-7 in a functionally important pathway that causes disease when it is dysregulated., Introduction Truncating and selected missense mutations in EPCAM (encoding epithelial cell adhesion molecule [EpCAM; CD326]) cause a severe autosomal recessive childhood diarrheal syndrome termed congenital tufting enteropathy (CTE) (1, 2). [...]

Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS-mediated increase in ICAM-1 and VCAM-1 expression, (P < 0.01) in HUVEC. Sulforaphane also prevented the LPS-mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P < 0.01). Stattic, a STAT3 inhibitor, reduced the LPS-induced expression of ICAM-1 and VCAM-1, and STAT3 phosphorylation (P < 0.01). STAT3 small interfering RNA treatment reduced the LPS-induced expression of ICAM-1, VCAM-1, and STAT3 (P < 0.01). Sulforaphane reduced LPS-mediated THP-1 monocyte adhesion to HUVEC (P < 0.01). In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, and this effect was prevented by sulforaphane. These data provide insight into the mechanism through which sulforaphane partly reduces the expression of ICAM-1 and VCAM-1 on the vascular wall by inhibiting STAT3 phosphorylation. Key words: sulforaphane, STAT3, ICAM-1, VCAM-1, endothelial cell. La molecule d'adhesion intercellulaire ICAM-1 et la molecule d'adhesion des cellules vasculaires VCAM-1 jouent un role cle dans l'initiation de l'inflammation vasculaire. Dans cette etude, les auteurs ont regarde si le sulforaphane, un compose phytochimique alimentaire, peut inhiber l'expression d'ICAM-1 et de VCAM-1 par les cellules endotheliales de cordon ombilical humaines (HUVEC) stimulees par le lipopolysaccharide (LPS), et examine le mecanisme implique. Le sulforaphane prevenait l'augmentation de l'expression d'ICAM-1 et de VCAM-1 induite par le LPS (P < 0,01) chez les HUVEC. Le sulforaphane prevenait aussi l'augmentation de la phosphorylation du transducteur de signal et activateur de transcription STAT3 induite par le LPS. Stattic, un inhibiteur de STAT3, reduisait l'expression d'ICAM-1 et de VCAM-1 ainsi que la phosphorylation de STAT3 induites par le LPS (P < 0,01). Un traitement avec un petit ARN interferent de STAT3 reduisait l'expression d'ICAM-1 et de VCAM-1 et la phosphorylation de STAT3 induites par le LPS (P < 0,01). Le sulforaphane reduisait l'adhesion des monocytes THP-1 aux HUVEC induite par le LPS (P < 0,01). Chez les souris C57BL/6, l'injection de LPS augmentait l'expression d'ICAM-1 et de VCAM-1 dans l'aorte, et cet effet etait inhibe par le sulforaphane. Ces donnees donnent un apercu du mecanisme a travers lequel le sulforaphane reduit partiellement l'expression d'ICAM-1 et de VCAM-1 sur la paroi vasculaire en inhibant la phosphorylation de STAT3. [Traduit par la Redaction] Mots-cles : sulforaphane, STAT3, ICAM-1, VCAM-1, cellule endotheliale., Introduction Cell adhesion molecules play a pivotal role in cancer and inflammatory diseases (Golias et al. 2007). Upregulation of adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) and vascular [...]

Byline: Yunlei. Pan, Shunli. Tang, Lina. Xu, Siting. Zheng, Jianjun. Qiao, Hong. Fang Sir, Psoriasis is characterized by exaggerated and disordered epidermal cell proliferation and keratinization. The impaired epidermal barrier [...]

: Introduction: HIV affects more women than any other life‐threatening infectious agent, and most infections are sexually transmitted. HIV must breach the female genital tract mucosal barrier to establish systemic infection, and clinical studies indicate virus more easily evades this barrier in women using depot‐medroxyprogesterone acetate (DMPA) and other injectable progestins for contraception. Identifying a potential mechanism for this association, we learned DMPA promotes susceptibility of wild‐type mice to genital herpes simplex virus type 2 (HSV‐2) infection by reducing genital tissue expression of the cell‐cell adhesion molecule desmoglein‐1 (DSG‐1) and increasing genital mucosal permeability. Conversely, DMPA‐mediated increases in genital mucosal permeability and HSV‐2 susceptibility were eliminated in mice concomitantly administered exogenous oestrogen (E). To confirm and extend these findings, herein we used humanized mice to define effects of systemic DMPA and intravaginal (ivag) E administration on susceptibility to genital infection with cell‐associated HIV‐1. Methods: Effects of DMPA or an intravaginal (ivag) E cream on engraftment of NOD‐scid‐IL‐2Rgc[sup.null] (NSG) mice with human peripheral blood mononuclear cells (hPBMCs) were defined with flow cytometry. Confocal microscopy was used to evaluate effects of DMPA, DMPA and E cream, or DMPA and the pharmacologically active component of the cream on vaginal tissue DSG‐1 expression and genital mucosal permeability to low molecular weight (LMW) molecules and hPBMCs. In other studies, hPBMC‐engrafted NSG mice (hPBMC‐NSG) received DMPA or DMPA and ivag E cream before genital inoculation with 10[sup.6] HIV‐1‐infected hPBMCs. Mice were euthanized 10 days after infection, and plasma HIV‐1 load quantified by qRT‐PCR and splenocytes used to detect HIV‐1 p24 antigen via immunohistochemistry and infectious virus via TZM‐bl luciferase assay. Results: Whereas hPBMC engraftment was unaffected by DMPA or E treatment, mice administered DMPA and E (cream or the pharmacologically active cream component) displayed greater vaginal tissue expression of DSG‐1 protein and decreased vaginal mucosal permeability to LMW molecules and hPBMCs versus DMPA‐treated mice. DMPA‐treated hPBMC‐NSG mice were also uniformly susceptible to genital transmission of cell‐associated HIV‐1, while no animal concomitantly administered DMPA and E cream acquired systemic HIV‐1 infection. Conclusion: Exogenous E administration reduces susceptibility of DMPA‐treated humanized mice to genital HIV‐1 infection., Introduction Women aged 15 to 24 years in sub‐Saharan Africa are especially vulnerable to HIV, and currently represent 25% of the new infections in the region. Reasons for this are [...]

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with demyelination and axonal loss. A whole genome association scan suggested that allelic variants in the CD58 gene region, encoding the costimulatory molecule LFA-3, are associated with risk of developing MS. We now report additional genetic evidence, as well as resequencing and fine mapping of the CD58 locus in patients with MS and control subjects. These efforts identify a CD58 variant that provides further evidence of association with MS (P = 1.1 x [10.sup.-6], OR 0.82) and the single protective effect within the CD58 locus is captured by the [rs2300747.sup.G] allele. This protective [rs2300747.sup.G] allele is associated with a dose-dependent increase in CD58 mRNA expression in lymphoblastic cell lines (P = 1.1 x [10.sup.-10]) and in peripheral blood mononuclear cells from MS subjects (P = 0.0037). This protective effect of enhanced CD58 expression on circulating mononuclear cells in patients with MS is supported by finding that CD58 mRNA expression is higher in MS subjects during clinical remission. Functional investigations suggest a potential mechanism whereby increases in CD58 expression, mediated by the protective allele, up-regulate the expression of transcription factor FoxP3 through engagement of the CD58 receptor, CD2, leading to the enhanced function of CD[4.sup.+]CD[25.sup.high] regulatory T cells that are defective in subjects with MS. genetic | human | RNAI quantitative trait | inflammation

Byline: Carolyn S. Calfee (1), Mark D. Eisner (2), Polly E. Parsons (3), B. Taylor Thompson (4), Edward R. Conner (1), Michael A. Matthay (5), Lorraine B. Ware (6) Keywords: Acute respiratory distress syndrome; Acute lung injury; Intracellular adhesion molecule-1; Pulmonary edema Abstract: Objective To determine if levels of soluble intercellular adhesion molecule-1 (sICAM-1), a marker of alveolar epithelial and endothelial injury, differ in patients with hydrostatic pulmonary edema and acute lung injury (ALI) and are associated with clinical outcomes in patients with ALI. Design, setting, and participants Measurement of sICAM-1 levels in (1) plasma and edema fluid from 67 patients with either hydrostatic pulmonary edema or ALI enrolled in an observational, prospective single center study, and (2) in plasma from 778 patients with ALI enrolled in a large multi-center randomized controlled trial of ventilator strategy. Results In the single-center study, levels of sICAM-1 were significantly higher in both edema fluid and plasma (median 938 and 545 ng/ml, respectively) from ALI patients compared to hydrostatic edema patients (median 384 and 177 ng/ml, P < 0.03 for both comparisons). In the multi-center study, higher plasma sICAM-1 levels were associated with poor clinical outcomes in both unadjusted and multivariable models. Subjects with ALI whose plasma sICAM-1 levels increased over the first 3 days of the study had a higher risk of death, after adjusting for other important predictors of outcome (odds ratio 1.48 95% CI 1.03--2.12, P = 0.03). Conclusions Both plasma and edema fluid levels of sICAM-1 are higher in patients with ALI than in patients with hydrostatic pulmonary edema. Higher plasma sICAM-1 levels and increasing sICAM-1 levels over time are associated with poor clinical outcomes in ALI. Measurement of sICAM-1 levels may be useful for identifying patients at highest risk of poor outcomes from ALI. Author Affiliation: (1) Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143-0111, USA (2) Divisions of Pulmonary and Critical Care Medicine and Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA (3) Division of Pulmonary and Critical Care Medicine, Department of Medicine, Fletcher Allen Health Care, University of Vermont, Burlington, VT, USA (4) Pulmonary/Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA (5) Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, CA, USA (6) Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA Article History: Registration Date: 16/07/2008 Received Date: 09/01/2008 Accepted Date: 09/07/2008 Online Date: 01/08/2008 Article note: The members of the NHLBI ARDS Clinical Trials Network are listed in the Appendix.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive (myo)fibroblast accumulation and collagen deposition. One possible source of (myo)fibroblasts is epithelial cells that undergo epithelial-mesenchymal transition (EMT), a process frequently mediated by TGF-[beta]. In this issue of the JCI, Kim et al. report that epithelial cell--specific deletion of [alpha]3 integrin prevents EMT in mice, thereby protecting against bleomycin-induced fibrosis (see the related article beginning on page 213). The authors propose a novel mechanism linking TGF-[beta] and [beta]-catenin signaling in EMT through integrin-dependent association of tyrosine-phosphorylated [beta]-catenin and pSmad2 and suggest targeted disruption of this interaction as a potential therapeutic approach., Idiopathic pulmonary fibrosis (IPF) is a progressive disorder of unknown etiology characterized by fibroblast accumulation, collagen deposition, and ECM remodeling leading to parenchymal destruction (1). Historically, inflammation has been viewed [...]

Neuroligins (NLs) are postsynaptic cell-adhesion molecules that are implicated in humans in autism spectrum disorders because the genes encoding NL3 and NL4 are mutated in rare cases of familial autism. NLs are highly conserved evolutionarily, except that no NL4 was detected in the currently available mouse genome sequence assemblies. We now demonstrate that mice express a distant NL4 variant that rapidly evolved from other mammalian NL4 genes and that exhibits sequence variations even between different mouse strains. Despite its divergence, mouse NL4 binds neurexins and is transported into dendritic spines, suggesting that the core properties of NLs are retained in this divergent NL isoform. The selectively rapid evolution of NL4 in mice suggests that its function in the brain is under less stringent control than that of other NLs, shedding light on why its mutation in autism spectrum disorder patients is not lethal, but instead leads to a discrete developmental brain disorder. autism | cell-adhesion molecule | neurexin | synapse

Adhesion molecules expressed by activated endothelial cells play a key role in regulating leukocyte trafficking to sites of inflammation. Resting endothelial cells normally do not express adhesion molecules, but cytokines activate endothelial cells to express adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1), which mediate leukocyte adherence to endothelial cells. We now show that endothelial cells express microRNA 126 (miR126), which inhibits VCAM-1 expression. Transfection of endothelial cells with an oligonucleotide that decreases miR-126 permits an increase in TNF-[alpha]-stimulated VCAM-1 expression. Conversely, overexpression of the precursor to miR-126 increases miR-126 levels and decreases VCAM-1 expression. Additionally, decreasing endogenous miR-126 levels increases leukocyte adherence to endothelial cells. These data suggest that microRNA can regulate adhesion molecule expression and may provide additional control of vascular inflammation. inflammation | nitric oxide | leukocyte | atherosclerosis

Junctional adhesion molecule (JAM) is involved in tight junction (TJ) formation in epithelial cells. Three JAMs (A, B, and C) are expressed in rat hepatocytes, but only rat JAM-A is present in polarized WIF-B cells, a rat-human hepatic line. We used knockdown (KD) and overexpression in WIF-B cells to determine the role of JAM-A in the development of hepatic polarity. Expression of rat JAM-A short hairpin RNA resulted in ~50% KD of JAM-A and substantial loss of hepatic polarity, as measured by the absence of apical cysts formed by adjacent cells and sealed by TJ belts. When inhibitory RNA-resistant human JAM-A (huWT) was expressed in KD cells, hepatic polarity was restored. In contrast, expression of JAM-A that either lacked its PDZ-binding motif (hu[DELTA]C-term) or harbored a point mutation (T273A) did not complement, indicating that multiple sites within JAM-A's cytoplasmic tail are required for the development of hepatic polarity. Overexpression of huWT in normal WIF-B cells unexpectedly blocked WIF-B maturation to the hepatic phenotype, as did expression of three huJAM-A constructs with single point mutations in putative phosphorylation sites. In contrast, hu[DELTA]C-term was without effect, and the T273A mutant only partially blocked maturation. Our results show that JAM-A is essential for the development of polarity in cultured hepatic cells via its possible phosphorylation and recruitment of relevant PDZ proteins and that hepatic polarity is achieved within a narrow range of JAM-A expression levels. Importantly, formation/maintenance of TJs and the apical domain in hepatic cells are linked, unlike simple epithelia. partitioning-defective polarity protein/atypical protein kinase C complex

Background and aims: To evaluate the safety and efficacy of the intercellular adhesion molecule 1 (ICAM-1) antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) in Crohn's disease. Methods: Active (CROHN'S disease activity [...]

Byline: B. Nohe (1), H.-J. Dieterich (1), M. Eichner (2), K. Unertl (1) Keywords: Key words Albumin; Endothelium; E-Selectin; ICAM-1; VCAM-1 Abstract: Objective: Increased levels of soluble adhesion molecules, a decreased PO.sub.2/FIO.sub.2 ratio and a tendency to worsened outcome have been reported following the use of human albumin in critical illness. The reasons are not yet understood. Since albumin solutions have previously been shown to contain proinflammatory mediators, a direct upregulation of adhesion molecules by contaminated batches may explain these findings. To examine this, we studied the effects of different albumin preparations on endothelial cell adhesion molecules in vitro. Design: Experimental study. Setting: Laboratory for cell biology. Methods: Human umbilical venous endothelial cell cultures (n = 4) were incubated for 6 h at 5 mg/ml with four different human albumin solutions (HA1--4) from different manufacturers. Medium served as the control. Using flow cytometry, the effects on E-selectin, ICAM-1 and VCAM-1 expression were determined on unstimulated cells and on cells stimulated with tumour necrosis factor [alpha] at 0.5 ng/ml for 4 h. Measurements and results: On unstimulated cells, HA1 and HA4, two different batches from the same manufacturer, increased ICAM-1 by 22 % and 15 %, respectively. After stimulation, both solutions resulted in a 19 % increased expression of E-Selectin. In addition, HA4 decreased VCAM-1 on stimulated cells (pa$? 0.05). Two albumin preparations from other manufacturers did not produce significant effects. Conclusions: Some albumin solutions directly modulate adhesion molecule expression on endothelial cells. This may, at least in part, explain the previous finding of increased soluble adhesion molecules and a decreased PO.sub.2/FIO.sub.2 ratio in critically ill patients undergoing volume replacement with human albumin. Author Affiliation: (1) Department of Anaesthesiology, University of Tuebingen, Hoppe-Seyler Strasse 3, D-72076 Tuebingen, Germany email: boris.nohe@uni-tuebingen.de Tel.: + 49-70 71-2 98 11 35 Fax: + 49-70 71-29 51 95, DE (2) Department of Medical Biometry, University of Tuebingen, Hoppe-Seyler Strasse 3, D-72076 Tuebingen, Germany, DE Article note: Received: 28 May 1999*Accepted: 14 September 1999

Byline: S. Gando (1), S. Nanzaki (1), Y. Morimoto (1), S. Kobayashi (1), O. Kemmotsu (1) Keywords: Key words Cardiac arrest; Cardiopulmonary resuscitation; Selectin; Neutrophil; Endothelium Abstract: Objective: To investigate the relationship between cytokines and the inflammatory responses in patients with out-of-hospital cardiac arrest, we examined the changes of cytokines as well as alterations in the markers of neutrophil activation, platelet and endothelial activation, and endothelial injury. Design: Prospective, cohort study. Setting: General intensive care unit of a tertiary care center. Patients and participants: 26 out-of-hospital cardiac arrest patients were classified into two groups: those who achieved return of spontaneous circulation (ROSC) (n = 10) and those with no ROSC (n = 16). Eight normal healthy volunteers served as control subjects. Measurements and results: Serial levels of soluble L-selectin (sL-selectin), soluble P-selectin (sP-selectin), neutrophil elastase, and soluble thrombomodulin were measured during and after cardiopulmonary resuscitation (CPR). Serial levels of tumor necrosis factor [alpha] (TNF[alpha]) and interleukin-1[beta] (IL-1[beta]) were also measured. We could not find any elevations in either cytokine during the study period. In both groups, sP-selectin levels were significantly higher than those in control subjects from the time of arrival at the emergency department to 24 h after admission. sL-selectin levels in the two groups were markedly lower compared to those in control subjects at all sampling points. In patients with ROSC, cardiac arrest and CPR led to an increase in the levels of neutrophil elastase and soluble thrombomodulin that peaked 6 h or 24 h after arrival at the emergency department. No statistical differences in the levels of the two selectins, neutrophil elastase, and soluble thrombomodulin between the two groups were found during CPR. Conclusions: Out-of-hospital cardiac arrest and CPR induces platelet, neutrophil, and endothelial activation and is associated with endothelial injury. Inflammatory cytokines may not have an important role in human whole-body ischemia-reperfusion injury. Author Affiliation: (1) Department of Anesthesiology and Intensive Care, Hokkaido University School of Medicine, N15 W7, Kita-ku, Sapporo, 060 Japan e-mail: sgando@med.hokudai.ac.jp Tel. +81(11)716--1161 Fax +81(11)716--9666, JP Article note: Received: 2 November 1998 Final revision received: 3 March 1999 Accepted: 26 March 1999

Byline: Naotomo Ohno (1), Hiroshi Ichikawa (1), Laura Coe (1), Peter R. Kvietys (2), D. Neil Granger (1), J. Steven Alexander (1) Abstract: We observed that normal plasma dramatically reduces neutrophil-endothelial adhesion. Therefore, we identified factors in plasma which might limit PMN adhesion in vitro. We found that the anti-adhesive effect was not mediated by vasoactive lipids present in plasma. Immunoprecipitation of soluble adhesion molecules, P and E-selectins and ICAM-1 restored PMN adhesion to control values. We further examined whether soluble adhesion molecules in plasma might also regulate PMN endothelial migration in response to fMLP (10.sup.-6 M). Plasma significantly reduced PMN migration, and this effect was prevented only by the simultaneous removal of soluble P and E selectins and ICAM-1 together, but not individually. These data show that soluble selectins and ICAM-1 may regulate PMN adhesion and diapedesis, and that alterations in the levels of these molecules may regulate PMN-endothelial interactions in vivo. Author Affiliation: (1) Department of Physiology, LSU Medical Center, Shreveport, Louisiana, 71130 (2) Victoria Hospital Research Institute, London, Ontario, Canada, N6A4G5 Article History: Registration Date: 04/09/2004

Diets rich in (n-3) polyunsaturated fatty acids (PUFA) are associated with suppression of the immune system, but the mechanisms are unclear. Specific immune responses are initiated by antigen-presenting cells. This study examines the in vitro effect of the (n-3) PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the expression of cell surface molecules required for normal antigen-presenting cell function on human blood monocytes. Monocytes were incubated with or without EPA or DHA for 48 h at 37 [degrees] C. Following incubation, expression of major histocompatibility complex (MHC) class II molecules (HLA-DR, -DP and -DQ) and adhesion molecules [intercellular adhesion molecule- 1 (ICAM-1) and leucocyte function associated antigen-1] was quantified by flow cytometry. in the presence of EPA alone there was a significantly lower median intensity of expression of HLA-DR and ICAM-1 relative to incubations without EPA. In contrast, significantly greater median intensities of expression of HLA-DR and -DP were observed following incubation with DHA. In parallel experiments, where monocytes were simultaneously activated by the addition of interferon-gamma to the cultures, median expression intensities of HLA-DR, -DP and ICAM-1 were significantly lower in the presence of either EPA or DHA compared with incubations without the (n-3) PUFA. These findings support previous animal studies that suggest that (n-3) PUFA can influence immune reactivity by modulating antigen-presenting cell function. INDEXING KEY WORDS: * (n-3) polyunsaturated fatty acids * major histocompatibility complex class II * monocytes * humans * adhesion molecules