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Biomedical subjects

R M Strieter

Publications and source records attributed to R M Strieter.

At least 271 records · Page 15Linked to original sources
PubMed1993

The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation.

Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a 6-8-kD, lipopolysaccharide-inducible monocyte and neutrophil chemotactic protein that may be important in acute and chronic inflammation. The present study determined the sequential production, source, and in vivo contribution of murine MIP-1 alpha in synchronized Schistosoma mansoni egg pulmonary granuloma formation. Granulomas were examined under conditions of primary, secondary vigorous, and secondary immunomodulated immunity. Secreted MIP-1 alpha was measured in 24-h supernatants from intact granulomas (700/ml) cultured with or without soluble egg antigen (SEA). Primary granulomas isolated from naive mice over a 16-d period showed low spontaneous MIP-1 alpha production (< 1 ng/ml). However, when primary granulomas were challenged with SEA, significant MIP-1 alpha production was observed beginning at day 4 and peaking at day 16. Intact vigorous (isolated from 8-wk-infected mice) and modulated (isolated from 20-wk-infected mice) secondary pulmonary granulomas demonstrated comparable spontaneous MIP-1 alpha production. Addition of SEA to vigorous stage granulomas augmented expression of MIP-1 alpha at all time points, whereas stimulated modulated stage granulomas did not increase production. The latter observation is likely related to endogenous immunoregulatory mechanisms reported for modulated stage animals. Immunohistochemical localization of MIP-1 alpha in granuloma sections and cytocentrifuge preparations from vigorous lesions localized MIP-1 alpha production to macrophages within granulomas. Treatment of mice with rabbit anti-mouse MIP-1 alpha antibodies significantly decreased 8-d primary granuloma formation (> 40%) when compared with control mice. Anti-MIP-1 alpha sera also decreased vigorous (> 20%), but not modulated granuloma formation. These findings demonstrate that MIP-1 alpha contributes to cellular recruitment during schistosome egg granuloma formation.

Animals↗
PubMed1993

MCP-1 expression by rat type II alveolar epithelial cells in primary culture.

Recruitment and activation of mononuclear phagocytes are potentially critical regulatory events for control of pulmonary inflammation. Located at the boundary between the alveolar airspace and the interstitium, alveolar epithelial cells are ideally situated to regulate the recruitment and activation of mononuclear phagocytes through the production of cytokines in response to inflammatory stimulation from the alveolar space. To test this hypothesis, we investigated the production of monocyte chemotactic polypeptide-1 (MCP-1), a protein that is chemotactic for and that activates monocytes, by rat type II alveolar epithelial cells in primary culture. Immunocytochemical staining using anti-murine JE, an antibody recognizing rat MCP-1, demonstrated cell-associated MCP-1 Ag throughout the monolayer. The intensity of staining was increased in response to IL-1 beta. When type II epithelial cells formed a tight monolayer on a filter support, there was polar secretion of MCP-1 Ag into the apical compartment by both control and IL-1-stimulated cells as measured by specific MCP-1 ELISA. Northern blot analysis revealed that IL-1 and TNF-alpha stimulated MCP-1 mRNA expression in a dose-dependent manner, whereas dexamethasone blocked MCP-1 expression by cells stimulated with IL-1. In contrast to previous results using transformed epithelial cell lines, MCP-1 mRNA was induced in these primary cultures directly by stimulation with LPS. These data suggest that alveolar epithelial cells may have an important and previously unrecognized role in the initiation and maintenance of inflammatory processes in the lung by recruiting and activating circulating monocytes through the production of MCP-1.

Animals↗
PubMed1993

The bimodal expression of tumor necrosis factor-alpha in association with rat lung reimplantation and allograft rejection.

Lung transplantation has become a therapeutic option for a number of end-stage pulmonary disorders. Lung transplant recipients experience more complications due to acute and chronic allograft rejection as compared to recipients of other solid organs. We postulated that the generation of TNF-alpha plays a significant role in the pathogenesis of acute lung allograft rejection. To test our hypothesis, we used a RT1-incompatible rat lung allograft model and demonstrated the time course, cellular source(s), and major compartment(s) of TNF production during the course of lung allograft rejection. This model allowed for immunogenetic standardization and reproducibility of lung allograft rejection across disparate major histocompatibility barriers. TNF production was characterized at the whole animal, organ, cellular, and molecular levels, and was found to be compartmentalized and expressed in a bimodal fashion from the lung allograft during lung allograft reimplantation and maximal rejection. Lung allograft rejection was significantly attenuated in animals pretreated with neutralizing TNF antisera as compared to animals receiving control sera. These findings may provide interesting insight into the use of novel and specific therapeutic intervention(s) during periods of acute lung allograft rejection.

Animals↗
PubMed1993

Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups.

Neutrophils have been implicated in the pathogenesis of the adult respiratory distress syndrome (ARDS). We have measured concentrations of the neutrophil attractant interleukin-8 in blood and bronchoalveolar lavage fluid (BAL) from patients at risk of ARDS. We studied 29 patients from three groups at risk of developing ARDS: multiple trauma (n = 16), perforated bowel (n = 6), and pancreatitis (n = 7). ARDS developed in 7 of these patients. Interleukin-8 in BAL and blood samples taken on initial hospital presentation was measured by a sandwich enzyme-linked immunosorbent assay. The mean BAL interleukin-8 concentration was significantly higher for the patients who subsequently progressed to ARDS than for the non-ARDS group (3.06 [SE 2.64] vs 0.053 [0.010] ng/mL, p = 0.0006). There was no difference between the groups in plasma interleukin-8 (6.23 [2.60] vs 5.12 [2.22] ng/mL, p = 0.31). Immunocytochemistry suggested that the alveolar macrophage is an important source of interleukin-8 at this early stage in ARDS development. This study provides evidence of a relation between the presence of interleukin-8 in early BAL samples and the development of ARDS. The early appearance of interleukin-8 in BAL of patients at risk of ARDS may be an important prognostic indicator for the development of the disorder and reinforces the likely importance of neutrophils and the effects of their accumulation and activation in the pathogenesis of many cases of ARDS.

Adolescent↗
PubMed1993

Inflammatory and procoagulant mediator interactions in an experimental baboon model of venous thrombosis.

Theoretic and in vitro evidence suggests that thrombosis and inflammation are interrelated. The purpose of the present study was to define the relationship between inflammation and deep venous thrombosis (DVT) in an in vivo model. Initiation of DVT was accomplished by administration of antibody to protein C (HPC4, 2 mg/kg) and tumor necrosis factor (TNF, 150 micrograms/kg); stasis; and subtle venous catheter injury. Thrombosis was assessed by thrombin-antithrombin assay (TAT), 125I-fibrinogen scanning (scan) over both the proximal and distal iliac veins, and ascending venography. Cytokines TNF, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8) were measured along with differential white blood cell counts, platelet counts, fibrinogen (FIB), and erythrocyte sedimentation rates (ESR). Baboon pairs were sacrificed on day 3 (T + 3d), T + 6d, and T + 9d and veins removed. All animals developed inferior vena cava and left iliofemoral DVT by venography; no right DVT was found. TAT was elevated by T + 1hr and peaked at T + 3hrs. Left iliofemoral DVT was found at T + 1hr by scan and reached a 20% uptake difference between the affected left and nonaffected right side at T + 3hrs. TNF peaked at T + 1hr; MCP-1 peaked at T + 6hrs; IL-8 and IL-6 peaked on T + 2d; all cytokines declined to baseline. TNF and TAT elevations were found to correlate with all cytokines; elevations in IL-8 were correlated with elevations in MCP-1 and IL-6 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Interferon-gamma regulation of human renal cortical epithelial cell-derived monocyte chemotactic peptide-1.

The chemoattractant signal(s) that results in the transmigration of monocytes/macrophage into the tubulointerstitium during acute inflammation is not known. Monocyte chemotactic peptide-1 (MCP-1), a recently described chemotactic cytokine, may function as both a potent monocyte chemotaxin and activator in renal inflammation. We have studied the proinflammatory conditions in which cultured human renal cortical epithelial cells (RCEC) of tubular origin may be stimulated to produce MCP-1. RCEC were stimulated in a dose-time dependent manner with: IL-1 beta (0.01 to 1.0 ng/ml), TNF (0.1 to 10 ng/ml), LPS (0.1 to 10 micrograms/ml) or INF-gamma (10-1000 U/ml). Conditioned media from RCEC stimulated with either IL-1 beta or INF-gamma produced a monocyte chemoattractant activity which was significantly suppressed with neutralizing antibody to MCP-1. Stimulation of RCEC with either IL-1 beta or INF-gamma resulted in a significant (4- to 5-fold) increase in steady state levels of MCP-1 mRNA. MCP-1 antigenic peptide in RCEC conditioned media was significantly increased over control (2- to 2.5-fold) after stimulation with either IL-1 beta or IFN-gamma. In contrast, production of interleukin-8 (IL-8), a neutrophil chemotactic cytokine, was not stimulated by IFN-gamma in RCEC. Thus, the chemokine signaling repertoire of renal tubule cells may be selectively controlled by IFN-gamma.

Base Sequence↗
PubMed1993

Role of tumor necrosis factor-alpha in disease states and inflammation.

OBJECTIVE: To review the animal and human data defining the role of tumor necrosis factor (TNF) in the pathogenesis of the septic shock syndrome, the systemic inflammatory response syndrome, and related pathologic states. DATA SOURCES: The international English language literature from 1975 to present formed the basis for this review. MEDLINE was used to identify pertinent animal and human studies. STUDY SELECTION: Those animal and human studies that focused on the mechanisms of action of TNF, its role in the inflammatory cytokine network, and the potential uses of anti-TNF therapies were emphasized. DATA EXTRACTION: Animal studies were selected based on the relevance of the model to the pathogenesis of the human systemic inflammatory response syndrome. Where they provided supportive evidence, human studies were selected on the basis of study design. DATA SYNTHESIS: TNF plays a major role in systemic inflammatory response syndrome secondary to infection, burns, trauma or hemorrhagic shock, and pancreatitis. TNF influences the outcome of other infectious processes, including allograft rejection, ischemia-reperfusion injury, delayed-type hypersensitivity, and granuloma development. The administration of anti-TNF antibodies, soluble TNF receptors, and related fusion proteins may limit organ damage and decrease mortality rate. CONCLUSIONS: Although the regulated release of TNF may exert normal physiologic effects, the uncontrolled production of TNF may lead to organ dysfunction and death. TNF mediates a variety of other physiologic processes that are unrelated to sepsis syndrome. New anti-TNF therapies appear to attenuate the injurious actions of TNF.

Animals↗
PubMed1993

Adherence in combination with lipopolysaccharide, tumor necrosis factor or interleukin-1 beta potentiates the induction of monocyte-derived interleukin-8.

In this study we demonstrate that adherence of peripheral blood mononuclear cells (PBMC) to either plastic or extracellular matrix, such as collagen type I or fibronectin, is a significant stimulus for the induction of both interleukin-8 (IL-8) mRNA and antigen. In addition, adherence of PBMC in the presence of lipopolysaccharide, interleukin-1-beta, or tumor necrosis factor-alpha greatly enhances transcription/translation of IL-8 from these leukocytes. Our findings demonstrate that PBMC adherent to either plastic or physiological surfaces in combination with an inflammatory agonist is both a potent and efficacious signal for the expression and production of the neutrophil chemotactic/activating cytokine, IL-8.

Base Sequence↗
PubMed1993

In situ expression of cytokines and cellular adhesion molecules in the skin of patients with systemic sclerosis. Their role in early and late disease.

Cytokines and cellular adhesion molecules (CAMs) may play a role in the inflammatory and fibrotic processes underlying systemic sclerosis (SSc). We compared the immunohistological distribution of cytokines and CAMs in skin biopsies from 12 SSc patients and 14 normal (NL) individuals. Among CAMs, vascular cell adhesion molecule-1 (VCAM-1), which mediates leukocyte-endothelial adhesion, showed increased expression on SSc versus NL endothelium and stratum granulosum. P-selectin was up-regulated in SSc versus NL stratum granulosum. The CD44 lymphocyte homing receptor showed the most striking differences between SSc and NL: its expression was increased in SSc stratum granulosum, stratum spinosum, on lymphocytes, and macrophages. Regarding cytokines, interleukin-6 (IL-6) expression was increased on SSc versus NL endothelium and fibroblasts. Tumor necrosis factor-alpha (TNF-alpha) reactivity was more prevalent in SSc than NL stratum granulosum, whereas IL-8 expression was higher on SSc compared to NL endothelium. Some CAMs, such as VCAM-1 and P-selectin, and cytokines, namely TNF-alpha and IL-8, were more commonly found in skin biopsies taken from early (< or = 1 year's duration) SSc, while others, such as IL-6, showed up-regulation in the late stage of the disease. The results suggest that certain CAMs and cytokines may play a differential role in both the early, inflammatory, and the late, fibrotic stage of SSc.

Adult↗
PubMed1993

Expression of interleukin-6 in association with rat lung reimplantation and allograft rejection.

Organ transplantation has become a therapeutic option for the replacement of malfunctioning tissues and organs. Since the advent of the first combined heart-lung transplant in 1981, there has been a rapid growth in the popularity of lung transplantation for a number of end-stage pulmonary disorders. Interestingly, these lung transplant patients experience more complications of acute and chronic allograft rejection compared with recipients of other solid organs. These episodes of rejection are related to a complex series of events that depend on the interaction of many cells and soluble mediators leading to cellular and tissue injury. The histopathology of lung allograft rejection has been actively studied and is associated with the sequestration of activated mononuclear phagocytes, T and B lymphocytes. These cells secrete a number of soluble mediators, that is, cytokines, that participate in the evolution of the immune response via autocrine, paracrine, or endocrine mechanisms. The interaction of cytokines with their targets leads to cellular activation, proliferation, and differentiation. In this study, we postulated that interleukin-6 (IL-6) may have a central role in the pathogenesis of acute lung allograft rejection. To test this hypothesis, we employed an unmodified RT1-incompatible rat lung allograft model and assessed the time course and major tissue compartment(s) of IL-6 production during the evolution of lung allograft rejection. The expression and production of IL-6 during the pathogenesis of lung allograft rejection was measured at the whole-animal, organ, cellular, and molecular levels. The expression of IL-6 was found to be bimodal in character, initially related to the reimplantation response and finally to the maximal allograft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Interleukin-1 receptor antagonist expression in sarcoidosis.

Sarcoidosis is a systemic granulomatous disease with a marked propensity for involvement of the pulmonary parenchyma and thoracic lymphatic system. This granulomatous process is characterized by aggregations of mononuclear cells, multinucleated giant cells, and variable degrees of fibrosis. The agent(s) responsible for the initiation of the inflammatory granulomatous process remain unknown. Interleukin-1 beta (IL-1) is a cytokine that has been shown to possess potent proinflammatory properties and is likely to play a role in mediating many of the immunopathologic events observed in sarcoidosis. Despite the degree of granulomatous inflammation, both the pulmonary and systemic pathogenic changes associated with sarcoidosis have a remarkable propensity for spontaneous resolution. The interleukin-1 receptor antagonist (IRAP), an endogenous inhibitor of IL-1 bioactivity, may have a critical role as an in vivo immunomodulator of IL-1-dependent granulomatous inflammation of sarcoidosis. In this study we demonstrate constitutive expression of IRAP mRNA and antigen from bronchoalveolar lavage fluid cells and cell-free fluid, respectively, obtained from both normal subjects and patients with sarcoidosis. However, immunolocalization of IRAP was found to be significantly localized to the sarcoid granuloma as compared with the uninvolved lung interstitium. Our findings indicate that IRAP expression is compartmentalized (granuloma) within the interstitium of patients with sarcoidosis. Thus, IRAP may function as an important in vivo immunomodulator of granulomatous inflammation.

Adult↗
PubMed1993

Gene expression of macrophage inflammatory protein-1 alpha from human blood monocytes and alveolar macrophages is inhibited by interleukin-4.

Mononuclear phagocytes are essential cellular mediators of both acute and chronic inflammatory responses. In addition to producing substances that mediate tissue injury directly, such as proteolytic enzymes and oxygen radical species, mononuclear phagocytes can secrete proteins involved in the activation and recruitment of inflammatory cells. One of the major inducible polypeptides secreted by mononuclear phagocytes is macrophage inflammatory protein 1 (MIP-1). Native MIP-1 is a protein with leukocyte chemotactic and stimulatory activity. MIP-1 consists of two highly homologous peptides, MIP-1 alpha and MIP-1 beta. We now characterize the expression of MIP-1 alpha from human peripheral blood monocytes (PBM) and identify the T-lymphocyte product interleukin-4 (IL-4) as an important regulator of MIP-1 alpha expression from PBM. In initial experiments, we demonstrated the production of MIP-1 alpha from lipopolysaccharide (LPS)-, interleukin-1 (IL-1)-, and phytohemagglutinin (PHA)-stimulated PBM. IL-4 inhibited the production of MIP-1 alpha from LPS-, IL-1-, and PHA-challenged PBM by 63, 81, and 88%, respectively. The suppressive effects of IL-4 were operative at the level of MIP-1 alpha mRNA, which was reduced in a dose-dependent fashion by IL-4. The suppression of MIP-1 alpha mRNA by IL-4 was observed within a narrow temporal window and was dependent upon the de novo synthesis of a protein intermediate. As determined by mRNA stability studies, IL-4 decreased steady-state levels of MIP-1 alpha mRNA, in part, by accelerating MIP-1 alpha mRNA decay.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1993

The production of chemotactic cytokines in an allogeneic response. The role of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3.

The in vitro mixed lymphocyte reaction (MLR) is regarded as a model of responsiveness to allogeneic major histocompatibility complex antigens and has historically been used to elucidate the pathway of T lymphocyte proliferation. In addition, the MLR response may reflect activation pathways relevant in acute allograft rejection. In the present study, we have applied the MLR to examine the role of adhesion molecules intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3 in the induction of tumor necrosis factor-alpha (TNF-alpha) as well as chemotactic cytokines, interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha). Monoclonal antibodies to the adhesion molecules (5 micrograms/ml) were added to one-way human MLR cultures and supernatants collected at various time points. The monoclonal antibodies to the adhesion molecules significantly suppressed the proliferative response by 50 to 80%. Cytokine production, TNF-alpha (3.2 +/- 0.5 ng/ml), MIP-1 alpha (12.9 +/- 3.3 ng/ml), MCP-1 (18.8 +/- 3.4 ng/ml), and IL-8 (57 +/- 18 ng/ml) peaked on day 5 of the assay. The addition of anti-intercellular adhesion molecule-1 to the cultures suppressed TNF-alpha, MIP-1 alpha, MCP-1, and IL-8 production by 68% (1.05 +/- 0.29 ng/ml), 85% (2.0 +/- 1.2 ng/ml), 63% (6.8 +/- 2.9 ng/ml), and 47% (30.3 +/- 3.7 ng/ml), respectively. Likewise, the addition of anti-lymphocyte function-associated antigen-3 monoclonal antibody suppressed the cytokines by 78% (0.71 +/- 0.34 ng/ml), 66% (4.5 +/- 2.2 ng/ml), 52% (8.8 +/- 2.2 ng/ml), and 73% (15.7 +/- 4.4 ng/ml), respectively. Immunohistochemical staining indicated that monocytes were the primary source of the chemokines IL-8, MCP-1, and MIP-1 alpha. The addition of exogenous recombinant TNF-alpha (5 ng/ml) or recombinant IL-2 (5 units/ml) to the anti-intercellular adhesion molecule-1-treated cultures allowed the recovery of the proliferative response as well as restoration of IL-2, TNF-alpha, and IL-8, but not MCP-1 or MIP-1 alpha, indicating that both soluble and adhesion molecule signals are required for the production of the C-C family of chemokines in allogeneic responses. Thus, the events resulting in cellular proliferation and chemokine production were dependent on adhesion molecule interactions.

Antibodies, Monoclonal↗