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M Patarroyo

Publications and source records attributed to M Patarroyo.

At least 55 records · Page 3Linked to original sources
PubMed1991

Increased susceptibility of IFN-gamma-treated neuroblastoma cells to lysis by lymphokine-activated killer cells: participation of ICAM-1 induction on target cells.

We have investigated the effect of interferon-gamma (IFN-gamma) treatment of neuroblastoma cells on the susceptibility to lysis by lymphokine-activated killer (LAK) cells and examined the participation of cell-adhesion molecules on the target cells in LAK cell lysis. Untreated neuroblastoma cells expressed lymphocyte-function-associated antigen 3 (LFA-3) and neural-cell-adhesion molecule (NCAM), but did not express MHC-class-I, MHC-class-II, or intercellular-adhesion molecule I (ICAM-I). IFN-gamma treatment of neuroblastoma cells induced the expression of MHC-class-I and ICAM-I antigens, but did not affect the expression of MHC-class-II, LFA-3, and NCAM. This was accompanied by an increased susceptibility to lysis by LAK cells. Anti-ICAM-I antibody inhibited partially the increased sensitivity of IFN-gamma-treated neuroblastoma cells to LAK cell lysis, and blocked completely the increase in binding of LAK cells observed after IFN-gamma treatment of the target cells. These results suggest that the increased LAK sensitivity of IFN-gamma-treated neuroblastoma cells is partially attributable to the induction of ICAM-I on neuroblastoma cells and indicate that post-binding events also play a role in the increased sensitivity to LAK cell lysis observed after IFN-gamma treatment.

Cell Adhesion Molecules↗
PubMed1991

[Leukocyte adhesion: a fundamental process in immunologic and inflammatory reactions].

Adhesion to cells and extracellular matrices is a fundamental feature of leukocyte physiology, a process crucial to the generation of immune and inflammatory responses. Adhesive interactions between lymphocytes, monocytes/macrophages, granulocytes and vascular endothelial cells are mediated by specific cell-adhesion molecules (CAMs). The Leu-CAMs (CD111/CD18) belong to a large family of cell-surface molecules known as intergrins, a family which also includes receptors for extracellular matrix components. In man, inherited deficiency of Leu-CAMs is characterised by recurrent, sometimes fatal, bacterial infections. In animals, on the other hand, Leu-CAM blocking by monoclonal antibodies has been found beneficial in inflammatory disorders. As some lymphoid malignancies are devoid of CAMs, it is possible that their absence may be a contributing factor in the development of leukaemia and lymphoma.

Antibodies, Monoclonal↗
PubMed1991

Role of the adhesion molecule ICAM-1 (CD54) in staphylococcal enterotoxin-mediated cytotoxicity.

Staphylococcal enterotoxin A (SEA) binds to major histocompatibility complex (MHC) class II molecules on target cells and directs human cytotoxic T lymphocytes (CTL) of irrelevant nominal specificity to mediate strong cytotoxicity against target cells. In this report we describe the importance of ICAM-1 (CD54) expression on the target cell in SEA-dependent cell-mediated cytotoxicity (SDCC), utilizing murine L cells co-transfected with HLA-DR and ICAM-1. Human CTL mediated a low but significant cytotoxicity against HLA-DR2- and HLA-DR7-transfected cells after preincubation with SEA, but no reactivity towards uncoated HLA-DR2 and HLA-DR7 cells or SEA-coated ICAM-1-transfected and untransfected L cells. In contrast, a strong cytotoxic response was mediated by CTL against L cells co-transfected with HLA-DR2/ICAM-1 and HLA-DR7/ICAM-1. Similar cytotoxic activity of the CTL was seen at a 30-fold lower effector-to-target cell ratio when comparing the HLA-DR2/ICAM-1-expressing cells with the HLA-DR2-expressing cells. SEA dose-response analysis demonstrated that the HLA-DR2/ICAM-1-expressing target cells enabled the CTL to respond to a 1000-fold lower concentration of SEA in comparison to the HLA-DR2-expressing cells. CD3+CD4+ and CD3+CD8+ cytotoxic T cell lines were equally dependent on the expression of ICAM-1 on the target cell. The strong CTL activity against HLA-DR2/ICAM-1-transfected cells could be blocked by anti-CD11a or anti-CD18 monoclonal antibodies (mAb), but not by anti-CD11b, anti-CD11c, anti-CD2 or unrelated control mAb. The great sensitivity of HLA-DR2/ICAM-1 expressing target cells to SDCC was strongly reduced by preincubation with various anti-ICAM-1 mAb but not by mAb against monomorphic HLA-DR or murine MHC class I determinants. The result in this study clearly demonstrates that efficient re-targeting of human CTL by SE is dependent on a proper interaction with the heterodimer CD11a/CD18 (Leu-CAMa, LFA-1) on the CTL and its target cell ligand ICAM-1.

Antibodies, Monoclonal↗
PubMed1991

The expression of human intercellular adhesion molecule-2 is refractory to inflammatory cytokines.

The beta 2-integrin CD11a/CD18 binds to the intercellular adhesion molecules (ICAM)-1 (CD54) and ICAM-2. ICAM-1 has a wide distribution, and its expression is up-regulated by various cytokines. In contrast, ICAM-2 has a more restricted distribution, and is mainly expressed on endothelial cells. In the present study we show that it is not induced by inflammatory cytokines or other treatments on any of several cells studied. Moreover, antibodies to the intercellular adhesion ligands were not able to block all CD11a/CD18-dependent adhesion, indicating the presence of additional CD11a/CD18 ligands.

Antigens, CD↗
PubMed1991

Phosphorylation of the beta-subunit of CD11/CD18 integrins by protein kinase C correlates with leukocyte adhesion.

Adhesion of activated leukocytes to cells is of critical functional importance. The adhesion is known to be mediated mainly by the CD11/CD18 integrins, also known as leukocytic cell adhesion molecules, or Leu-CAM. We have now studied the phosphorylation of Leu-CAM by protein kinase C and the correlation of phosphorylation with the generation of the adhesive phenotype among human peripheral blood mononuclear leukocytes during cell activation. We here show that a good correlation exists between the phosphorylation of the beta subunit of Leu-CAM (CD18), and the extent of cell-to-cell adhesion. The phosphorylated CD18 subunit was associated with both CD11a and CD11b. Purified protein kinase C was able to phosphorylate the beta subunit of isolated Leu-CAM in vitro. The phosphorylation occurred mainly on serine residues.

Antigens, CD↗
PubMed1991

Calcium signaling capacity of the CD11b/CD18 integrin on human neutrophils.

The CD11b/CD18 integrin is a major cell adhesion molecule of myelomonocytic cells. Exposure of human neutrophils in suspension to CD11b or CD18 monoclonal antibodies (mAbs)2 does not affect the resting level of cytosolic free Ca2+ in these cells; however, a subsequent cross-linking of either of these antibodies triggers a prompt and significant cytosolic-free Ca2+ transient lasting about 10 min. The rise in cytosolic-free Ca2+ (from 130 +/- 2 to 414 +/- 12 nM or 111 +/- 12 to 331 +/- 22 nM caused by cross-linking of CD11b or CD18 subunits, respectively) is due to both mobilization of Ca2+ from intracellular stores and influx of Ca2+ across the plasma membrane. Cross-linking of the common leukocyte antigen (CD45) did not alter the basal level of cytosolic free Ca2+. In accordance with other adherence-induced phenomena and with CD11/CD18-mediated phagocytosis, these Ca2+ signals were only modestly affected by pertussis toxin. Thus, the present data clearly indicate that the CD11b/CD18 integrin on human neutrophils is capable of inducing a prompt cytosolic-free Ca2+ signal. These findings directly support the recent suggestion that the CD11b/CD18 integrin is responsible for the "spontaneous oscillations" of cytosolic-free Ca2+ observed in adherent neutrophils and, at least partially, also explain how integrin-mediated adherence can modify the functional responsiveness of neutrophils to a subsequent agonist stimulation.

Antigens, CD↗
PubMed1991

Leukocyte adhesion in host defense and tissue injury.

During their life span, leukocytes adhere transiently to one another, to other cell types, such as vascular endothelial cells, and to extracellular matrix proteins. This adhesiveness is mediated by families of specific cell surface adhesion molecules, namely, integrins, immunoglobulin superfamily molecules, and selectins. Adhesion is required for leukocyte-mediated cytotoxicity, phagocytosis, chemotaxis, and induction of lymphocyte proliferation and maturation. It also participates in recirculation and homing of lymphocytes into lymphoid organs and in leukocyte migration from the vascular compartment to extravascular tissues. Adhesion underlies the beneficial or detrimental role of leukocytes in immune and inflammatory responses. In animals, blocking monoclonal antibodies to adhesion molecules dramatically reduce vascular and tissue injury in several organs following ischemia-reperfusion, and delay renal allograft rejection. Moreover, expression of particular adhesion molecules is induced or increased in cells which are targets for allergic or autoimmune reactions and in inflamed tissues. On the other hand, a congenital deficiency of the CD11/CD18 integrins (Leu-CAMs) leads to recurrent, and sometimes fatal, bacterial infections, and lack of particular cell-adhesion molecules on Burkitt's lymphoma cells may enable these cells to escape immunosurveillance.

Cell Adhesion↗
PubMed1991

Ethanol impairs certain aspects of neutrophil adhesion in vitro: comparisons with inhibition of expression of the CD18 antigen.

Since ethanol impairs polymorphonuclear leukocyte (PMNL) delivery to inflammatory sites, the effect of ethanol on PMNL adhesiveness was studied in vitro. Ethanol inhibited PMNL aggregation induced by formylmethionylleucylphenylalanine (FMLP) but not by phorbol myristate acetate (PMA), whereas responses to both stimuli were abolished by treating PMNL with monoclonal antibody 60.3 (against the adhesion protein CD18). This antibody also abrogated spontaneous and FMLP-stimulated PMNL adhesion to plastic, whereas ethanol reduced spontaneous but not FMLP-induced adherence. Chemotaxis in Boyden or agarose systems was not diminished by ethanol, but high concentrations of MAb 60.3 inhibited migration under agarose. Nonetheless, upregulation of cell surface expression of CD18 (assessed by immunofluorescence flow cytometry) induced by FMLP or PMA was similarly reduced by ethanol. Thus, ethanol inhibited only certain of PMNL adhesion, and although the stimulated up-regulation of CD18 expression was reduced it is unlikely that ethanol effects were mediated only by this inhibition.

Antigens, CD↗
PubMed1991

The Epstein-Barr virus BNLF-1 membrane protein LMP1 induces homotypic adhesion mediated by CD11a/CD18 in a murine B-cell line, mimicking the action of phorbol ester.

Expression of the Epstein-Barr virus BNLF1 gene (LMP1) or treatment with 4B-phorbol-12,13-dibutyrate in the murine pro-B-cell line A/J-95 leads to a five- to sevenfold enhancement of homotypic adhesion without significant changes in adhesion molecule expression. Antibody to CD11a inhibits aggregation, indicating that CD11a/CD18-mediated adhesion is a common target for both agents.

Animals↗
PubMed1990

Participation of CD11a-c/CD18, CD2 and RGD-binding receptors in endogenous and interleukin-2-stimulated NK activity of CD3-negative large granular lymphocytes.

The effect of RGD-sequence-containing pentapeptides and monoclonal antibodies (MAbs) against the adhesion molecules CD11a-c/CD18, ICAM-1 (CD54) and CD2 on the binding and cytotoxicity of endogenous (freshly purified) and IL-2-stimulated CD3-negative NK cells has been studied. Antibody to CD18 exerted the most significant inhibition of adhesion and cytotoxicity of endogenous NK cells to MOLT-4 lymphoma cells, followed by antibodies to CD2 and CD54. Antibodies to either CD11a, CD11b or CD11c did not inhibit adhesion when used separately, whereas as a mixture their inhibitory capacity was as strong as that of anti-CD18. Antibodies against CD18, CD54 and CD2 exerted an additive effect on the inhibition of adhesion. Their combination eradicated the binding of endogenous NK cells. The RGD-containing peptide did not inhibit the binding or cytotoxicity of freshly purified NK cells to MOLT-4, whereas some inhibition was detected against the adenocarcinoma cell line COLO-205. According to FACS analysis, IL-2 increases the expression of CD2 and CD54 on NK cells. However, the relative contribution of the adhesion molecules to the NK cell binding did not change as a result of the stimulation with IL-2. The RGD-peptide substantially inhibited the binding of IL-2-stimulated killer cells to COLO, and the combination of this peptide with MAbs to CD18, CD54 and CD2 practically blocked the adhesion. Our results indicate that both CD11a-c/CD18- (involving the 3 heterodimers) and CD2-dependent adhesion pathways are used by LGL in endogenous and IL-2 stimulated natural killing. In addition, RGD-binding receptors are involved in adhesion to some target cells.

Antigen-Antibody Reactions↗
PubMed1990

The pivotal role of the Leu-CAM and ICAM molecules in human leukocyte adhesion.

Cellular adhesion is of fundamental importance in leukocyte physiology. It is a complex, strictly regulated process, which involves the participation of several cell surface glycoproteins. Among the most important are the Leu-CAMs or the CD11/CD18 integrin receptors, and their adhesion ligands ICAM-1 (CD54) and ICAM-2. In this review we summarize some recent work on various aspects of these molecules.

Antigens, CD↗
PubMed1990

The leukocyte adhesion glycoprotein CD18 participates in HIV-1-induced syncytia formation in monocytoid and T cells.

mAb 60.3 and IB4 to CD18, the common beta-subunit of the human leukocytic cell adhesion molecule family, efficiently inhibit syncytium formation induced by the interaction of HIV type 1 (HIV-1)-infected monocytoid cells and CD4+ T cells. The antibodies also interfere with cellfree HIV-1 infection of U-937 clone 16 cells. Virus-induced aggregation of these cells and the subsequent syncytia formation leading to massive cell death are efficiently blocked, and the number of infected cells remains at a very low level, 2 to 5%, for the entire culture period. However, anti-CD18 mAb do not inhibit binding of the viral envelope glycoprotein gp120 to the cell surface receptor CD4. The results indicate participation of CD18, or of the protein complex CD11a-c/CD18, in addition to CD4, in the infection and cytopathic effect of HIV-1. They also suggest that intercellular adhesion contributes to virus transmission from cell to cell and may be an important mechanism for virus spreading.

Antibodies, Monoclonal↗
PubMed1990

Expression of the adhesion molecule ICAM-1 and major histocompatibility complex class I antigens on human tumor cells is required for their interaction with autologous lymphocytes in vitro.

In a group of 30 human tumors, comprising 12 lung, 14 ovarian, 2 breast carcinomas, 1 hypernephroma and 1 mid-gut carcinoid, the expression of major histocompatibility complex (MHC) class I molecules and the intercellular adhesion molecule 1 (CAM-1, CD54) was found to vary independently. Some tumors expressed both or neither of these molecules. Among 9/13 ICAM-1+ tumors, in which greater than 50% cells reacted with the anti-ICAM-1 monoclonal antibody (mAb) (LB-2), the class I antigen was also detected on greater than 50% of the cells. Only 2 ICAM-1+ tumors were class-I-. In 5/17 cases the tumors were MHC-class-I+ and ICAM-1-. Lymphocytes collected from the blood or from the tumor site were assayed for recognition on the tumor cells in the auto-tumor cytotoxicity test and in mixed lymphocyte tumor cell culture (MLTC). Positive results were obtained only with the MHC-class-I+/ICAM-1+ tumors. In vitro treatment of the tumor cell suspensions with interferon gamma and tumor necrosis factor alpha (TNF alpha) induced or enhanced the ICAM-1 and/or class I antigen expression in 8/12 cases. Of the tumor samples treatged, 8/9 acquired stimulatory capacity and 3/10 became susceptible to lysis by the lymphocytes. In 6/6 MLTC performed with the cytokine-treated tumor cells, cytotoxicity against the autologous tumor was generated. Three of these MLTC lymphocytes also lysed the untreated targets. mAb directed to class I antigens or to ICAM-1 inhibited both the stimulation by and the lysis of tumor cells when confronted with fresh lymphocytes. The cytotoxicity generated in the MLTC was also inhibited. If, however, the cytotoxic function was induced in MTLC containing interleukin-2 (5 U/ml), inhibition was obtained only by pretreatment of the targets with mAb against ICAM-1. The results show thus (a) that the lymphocytes react in vitro with tumor cells only if these express both MHC class I molecules and ICAM-1; (b) that expression of these molecules can be induced by interferon alpha and TNF alpha; (c) that cytotoxic effectors generated in the MLTC with cytokine-treated tumors can also act on the untreated tumor cells. The requirement of the two surface moieties for the interaction with lymphocytes was also substantiated by blockade with relevant mAb.

Antibodies, Monoclonal↗
PubMed1990

Functional characteristics of the intercellular adhesion molecule-1 (CD54) expressed on cytotoxic human blood lymphocytes.

We have shown that intercellular adhesion molecule-1 (ICAM-1) (CD54) positive cells are mainly responsible for the natural cytotoxic function of human blood lymphocytes. The evidences were the inhibition of cytotoxicity by anti-ICAM-1 (LB-2) monoclonal antibodies (mAb) and the loss of lytic activity after removal of the ICAM-1+ cells. In addition, the cytotoxic potential of the separated ICAM-1- lymphocyte population after activation appeared in parallel with the expression of this molecule. The ICAM-1+ lymphocytes lysed both LFA-1 (CD11a/CD18 or Leu-CAMa) positive and negative cell lines, and pretreatment of the effectors with the LB-2 mAb also inhibited the lysis of LFA-1- targets. The results point to a yet unrecognized role of ICAM-1 on the lymphocytes. Kinetics experiments suggested that pretreatment of lymphocytes with alpha-ICAM-1 (LB-2) mAb did not inhibit the promptly established lytic interactions but influenced later events, recycling and/or recruitment of effectors. It is possible that the cytotoxic potential is regulated by contacts between the members of the lymphocyte population and that these events occur via their ICAM-1 and LFA-1. Exposure of lymphocytes to NK-sensitive targets for 16 hr elevated their cytotoxic potential. The function of activated lymphocytes was not inhibited by the LB-2 mAb.

Antibodies, Monoclonal↗
PubMed1990

Rabbit leukocyte adhesion molecules CD11/CD18 and their participation in acute and delayed inflammatory responses and leukocyte distribution in vivo.

In humans the glycoprotein complexes CD11/CD18 mediate leukocyte adhesion to cells. Mouse monoclonal antibodies (mAb) 60.3, 7E4, and IB4 to human CD18, found to cross-react with rabbit white blood cells, were used to identify the antigen in rabbit cells and to study adherence of rabbit leukocytes in vitro and in vivo. These antibodies labeled almost all unfractionated rabbit blood leukocytes and immunoprecipitated surface glycopolypeptides with apparent molecular weights of 85,000 and 150,000 from these cells. Adhesion of purified rabbit polymorphonuclear cells (PMNs) to cultured vascular endothelial cells in the presence of phorbol ester was blocked by the antibodies in a dose-dependent manner. The acute inflammatory response characterized by local accumulation of PMNs and concomitant plasma extravasation following intradermal injections of zymosan-activated serum (ZAS) in rabbits was inhibited in animals pretreated intravenously with anti-CD18 mAb. Intravital microscopy of the rabbit tenuissimus muscle demonstrated that anti-CD18 mAb. Intravital microscopy of the rabbit tenuissimus muscle demonstrated that anti-CD18 treatment specifically blocked the adhesion of activated leukocytes to the venular endothelium and thereby the subsequent diapedesis of these cells into the extravascular space. The lymphocyte-dependent tissue swelling resulting from a delayed-type hypersensitivity reaction in the rabbit ear was partially inhibited by anti-CD18 mAb. Systemic anti-CD18 treatment induced a pronounced increase in the number of circulating mononuclear and polymorphonuclear cells with a maximum at 24 hr after injection of the antibody. It is concluded that GP150/GP85 is the rabbit homologue of human CD11/CD18, and that leukocyte-cell adhesion mediated by these glycoprotein complexes participates in acute and delayed inflammatory responses and leukocyte distribution in vivo.

Animals↗
PubMed1990

Rapid adhesive responses of endothelial cells and of neutrophils induced by leukotriene B4 are mediated by leucocytic adhesion protein CD18.

Controversy has existed as to the ability of leukotriene B4 (LTB4) to enhance adhesive properties of human neutrophils (PMN) and endothelial cells. We found that LTB4 induced a rapid but transient adhesion of PMN to an albumin-coated plastic surface and to cultured human umbilical vein endothelial cells (HUVEC). Although the adhesive response of PMN to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) was longer lasting, peak hyperadherence was of similar magnitude as to LTB4 and was less susceptible to assay conditions. Adherence induced by either LTB4 or fMLP could be abrogated by the monoclonal antibody 60.3, indicating similar dependence on the leucocyte adhesion protein CD18. Lipoxin A did not induce PMN hyperadherence. Treating HUVEC with LTB4, but not with its omega-oxidized metabolites 20-OH- and 20-COOH-LTB4, lipoxin A, or with fMLP conferred a rapid, dose-related, enhanced adhesion of PMN. This effect was dependent on CD18 and on divalent cations. It disappeared with prolonged exposure to LTB4, required a metabolically active HUVEC, and was not due to passive binding of LTB4 to HUVEC. Thus, LTB4 induces a transient expression of hyperadhesiveness in HUVEC as well as in neutrophils, and both effects are dependent on expression of CD18.

Antibodies, Monoclonal↗
PubMed1990

Participation of CD11a-c/CD18 and RGD-recognizing adhesion molecules in the binding of LGL to fibroblasts. Evidence for the role of CD11a in the fibroblast-mediated inactivation of NK cells.

We have previously shown that large granular lymphocytes (LGL) are inactivated by contact with natural killer (NK) resistant monolayer target cells. In this work we have analysed which adhesion molecules are involved in the binding of LGL to such targets, as exemplified by fibroblasts, and in the subsequent inhibition of their NK activity. The results indicate that antibodies against CD54 (intercellular adhesion molecule 1, ICAM-1), CD11a (leucocyte function antigen 1, LFA-1, alpha chain), and CD18 (common beta chain of the beta 2-integrin family) significantly (by 50%) reduce the binding of LGL onto inhibitory target cells. The matrix protein-based synthetic peptide RGD and anti-CD29 (the common beta chain of the beta 2-integrin family) antibodies also diminish the binding (by 35%). The effects of the antiadhesion molecule antibodies and the peptide are additive, the combination of both leading to an almost complete block of adhesion. It may be hypothesized that some of the binding-relevant adhesion molecules of the RGD-binding domain on LGL (CD29) may be involved in the delivery of the inactivating signal to the effector cell. Indeed, incubation of LGL with anti-CD11a antibodies, but neither with antibodies against other binding-relevant epitopes nor with RGD, significantly reduced their NK activity. The mechanism of the inactivation was similar to that induced by intact NK-resistant target cells. On the basis of the present results we suggest that the CD11a molecule is involved in the down-regulation of the NK activity of peripheral blood lymphocytes.

Antibodies, Monoclonal↗