Monocyte adhesion molecule expression in interstitial inflammation in patients with renal failure.

BACKGROUND: Patients with renal failure have an increased susceptibility to infections. We therefore studied the recruitment of monocytes and their expression of adhesion molecules CD11b and CD62L at the site of interstitial inflammation in patients with renal failure. Furthermore, we studied if the capacity of monocytes to up-regulate CD11b in interstitial inflammation was determined by the interstitial concentration of chemotactic factors. METHODS: Three intensities of interstitial inflammation (0, intermediate and intense) were established in skin blister chambers. Leukocyte count, CD11b/CD62L expression, monocyte chemotactic protein-1 (MCP-1) and blister activity in terms of CD11b mobilization were determined. RESULTS: The CD62L expression on monocytes was lower in the peripheral circulation in patients with renal failure compared with healthy subjects (P<0.005 and P<0.001). At the site of interstitial inflammation patients had a higher expression of CD62L (intermediate, P<0.05; intense, P<0.005). Furthermore, monocytes from patients had an impaired capacity to mobilize CD11b both in the peripheral circulation (P<0.005) and at the intermediate and intense sites of interstitial inflammation (P<0.005 and P<0.001, respectively) compared with cells collected from healthy subjects. We incubated monocytes in blister exudates, in order to explore whether this phenomenon is caused by cellular factors and/or to the interstitial concentration of chemotactic mediators. The expression of CD11b on monocytes from healthy blood donors incubated in blister exudates from either patients or healthy subjects in vitro was similar. The interstitial concentration of MCP-1 at the site of intermediate inflammation was significantly lower in patients with renal failure compared with the corresponding blister exudate collected from healthy subjects (P<0.05), but no differences were observed at the site of intense inflammation. Furthermore, neutralizing the action of MCP-1 in blister exudates with monoclonal antibodies did not have any impact on monocyte CD11b expression following incubation in blister exudates. CONCLUSION: These studies indicate that the impaired capacity of monocytes to mobilize CD11b at the site of inflammation in patients with renal failure is more dependent on constitutive cellular factors than the concentration of CD11b mobilizing factors in the interstitium.     

Additive effects of CD59 expression in Gal knockout mice in vitro but not in an ex vivo model

Abstract: Transgenic expression of the human complement regulatory molecule CD59 in mice and genetic deletion of the major xenoantigen galactose α 1,3 galactose (Gal KO) each resulted in partial protection of spleen cells from lysis by human serum. These protective effects were additive when the two genetic modifications were combined. However, when the effects of these genetic modifications were examined in an ex vivo model in which mouse hearts were perfused with human plasma, it was Gal KO which was the modification which determined protection. CD59 expression alone was not protective and CD59 expression in combination with Gal knockout did not result in a significant additional increase in protection over and above that provided by Gal knockout alone. The likely explanation for this discrepancy between the in vitro and ex vivo data is that the H2-K^b promoter used to drive CD59 expression results I in substantially less expression on endothelium than on spleen cells.     

Effects of hemorrhagic shock on endotoxemia and its molecular mechanism

AlthoughtherearegrowingevidencesindicatlugthatonlyweakendotoxemlaexistsintheearlystageafterhemorrhagicshockinhumanbeingsoranirnalsLI-3,antagonistsagainstendotoxinssuchasbacterlcldal/permeablllty--lucreproteinf'j,polymyxinBL4'andlactuloseL',exertsignificantprotectiveeffectsonthevictimsinshock.Thisseemsthatbacterlalendotoxinsplayanimportantroleinthedevelopmentofhemorrhagicshock.However,itremainsunclarifiedwhethertheroleofendotoxinsinshockisrelatedtotheincreaseofanIndividual'ssensitivitytoendot…     

Association of a 70-kDa tyrosine phosphoprotein with the CD16:ζ:γ complex expressed in human natural killer cells

The CD16: ζ: γ receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fcγ domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of ζ and γ are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the ζ subunit and the phospholipase C γ-1 and γ-2 isoforms. Here we show that CD 16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16:ζ:γ receptor complex, results in the tyrosine phosphorylation of a 70 kDa ζ-associated protein (pp70). Similarly, a 70-kDa ζ-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa ζ-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16:ζ:γ complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.     

Soluble CD30 in pediatric patients with atopic dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory skin disease in which a pathogenetic role of Th2 cells has been supposed. This study investigated the presence of soluble CD30 (sCD30), an activation marker of T-cell clones able to produce Th2-type cytokines, in sera from pediatric patients affected by AD ( n =25) with no symptoms of asthma or rhinitis. The severity of the disease was graded by both the SCORAD and Costa et al. clinical scoring systems. Serum levels of sCD30 were significantly higher in patients with AD in respect to both normal donors ( n =20) and urticaria patients ( n = 10), and a positive correlation between serum sCD30 and clinical score was found ( r =0.508; P =0.01) when AD patients were evaluated by Costa et al.'s method. Furthermore, a significant association ( r -=0.443; P =0.027) between sCD30 and serum levels of the soluble interleukin (IL)-2 receptor (sIL-2R) was observed in AD. The presence of high amounts of sCD30 in atopic patients seems to confirm the role of this molecule as an activation marker useful for in vivo evaluation of a Th2 immune response, and the correlation observed with both clinical score and sIL-2R levels indicates the role of sCD30 as an additional marker of disease activity in pediatric patients with AD.     

Subpopulation structure of human T lymphocytes studied with monoclonal antibody CD27

Institute of Immunology, Ministry of Health of Russian. (Presented by Academician of the Russian Academy of Medical Sciences R. V. Petrov.) Translated from Byulleten Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 11, pp. 506–508, November, 1992.     

Immunocytochemical characterization of large granular lymphocytes in normal cervix and HPV associated disease.

A quantitative immunocytochemical study of large granular lymphocytes (LGLs) in the normal cervix and in human papillomavirus (HPV) associated disease was performed using a panel of monoclonal antibodies which included those for LGL surface markers CD56, CD16, and CD57. Only CD56-positive cells were found within the ectocervical epithelium and these cells increased in number in cervical intraepithelial neoplasia (CIN) in comparison with normal cervix. Examination of serial sections and double labelling suggests that these cells are CD3+, CD8+, CD56+, CD16+. The observed increase in number of this subset was not associated specifically with HPV infection but was related to CIN. Lymphocytes expressing all three LGL markers were found in the stroma and CD16(+)-positive cells clustered around endocervical glands with occasional cells extending into the endocervical epithelium. These results indicate that a small subset of LGLs which express T-cell markers is increased in number in CIN. Cells expressing classical NK markers are restricted to the stroma and are not found within the ectocervical epithelium.     

Metabolic myocardial viability assessment with iodine 123-16-iodo-3-methylhexadecanoic acid in recent myocardial infarction: Comparison with thallium-201 and fluorine-18 fluorodeoxyglucose

The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18 fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methyl-hexadecanoic acid (MIHA) as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and to evaluate its contribution compared with the²⁰¹Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection²⁰¹T1 imaging, rest MIHA imaging and glucoseloaded FDG imaging were performed in 22 patients with recent myocardial infarction. Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75 of maximum uptake on stress²⁰¹T1 imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a)²⁰¹T1 activity during exercise, redistribution and reinjection and (b) MIHA up-take, using the two FDG thresholds most commonly considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that²⁰¹T1 reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85 and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively;P<0.05 vs other tests). The global predictive values of MIHA and²⁰¹T1 reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold (NS). When only the 177 severely hypoperfused segments were considered,²⁰¹T1 reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold), while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold,P<0.05 vs²⁰¹T1 reinjection). In all circumstances, MIHA was less specific than²⁰¹T1 reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA accurately detects the persistence of metabolic viability, but is not superior to²⁰¹T1.