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R M Strieter

Publications and source records attributed to R M Strieter.

At least 217 records · Page 12Linked to original sources
PubMed1995

Macrophage inflammatory protein-1 alpha expression in vivo and in vitro: the role of lipoteichoic acid.

Lipoteichoic acid (LTA), a component of the cell wall of most gram-positive bacteria, has been shown to play a significant role in the initiation and progression of bacterial infection. However, little is known of its position in the cytokine network involved in the induction and perpetuation of inflammation. In this study, we assessed whether the macrophage activating and chemotactic cytokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) was expressed in the setting of localized gram-positive infection. Furthermore, we determined whether LTA purified from either Staphylococcus aureus or Streptococcus pyogenes could induce the expression of MIP-1 alpha mRNA and protein from human blood monocytes. Immunohistochemical staining of human endocardial samples obtained from patients with acute S. aureus endocarditis revealed cell-associated MIP-1 alpha expression by neutrophils, macrophages, and fibroblasts. Treatment of human peripheral blood monocytes in vitro with LTA isolated from either S. aureus or S. pyogenes resulted in both the time- and dose-dependent expression of MIP-1 alpha mRNA. Similarly, staphylococcal and streptococcal LTA induced the dose-dependent production of MIP-1 alpha protein after 24 h in culture. These studies suggest that LTA may play an important role in triggering the recruitment and activation of leukocytes that characterizes the host response to gram-positive bacterial invasion.

Base Sequence↗
PubMed1995

Macrophage inflammatory protein-1 beta: a C-C chemokine in osteoarthritis.

The aim of this study was to determine whether the cytokine macrophage inflammatory protein-1 beta (MIP-1 beta) is present and functionally active in the arthritic joint. We used immunoassays and bioassays to assess the presence and function of MIP-1 beta using samples obtained from 62 arthritic patients. MIP-1 beta levels were increased in synovial fluids (SFs) from patients with osteoarthritis (OA) (18.0 +/- 8.9 ng/ml) (SD) compared to patients with rheumatoid arthritis (RA) 6.1 +/- 2.9 ng/ml) or other forms of arthritis (10.4 +/- 7.0 ng/ml) (P < 0.05). Levels of OA SF MIP-1 beta were significantly greater than OA or normal serum levels of MIP-1 beta. Anti-MIP-1 beta neutralized 28% of the chemotactic activity for monocytes found in OA SFs. Isolated OA synovial tissue fibroblasts did not constitutively produce MIP-1 beta but could be induced to express this chemokine upon exposure to tumor necrosis factor-alpha, interleukin-1 beta, or lipopolysaccharide. Synovial tissue immunohistochemical staining revealed that the main immunopositive cells in OA were the lining cells as well as vascular smooth muscle and endothelial cells. A minority of macrophages were immunopositive as well. In this study, we identify MIP-1 beta as a unique cytokine increased in OA compared to RA SF. We conclude that MIP-1 beta may play a role in the ingress of monocytes into the OA joint.

Arthritis↗
PubMed1995

Regulation of monocyte-derived interleukin 1 receptor antagonist by cisplatinum.

IL-1 biology has taken on a new dimension with the discovery of the IL-1 receptor antagonist (IL-1ra). The balance in the production of monocyte-derived IL-1 and IL-1ra may impact on subsequent IL-1-dependent inflammation. Cancer patients are known to have impaired monocyte biological function. Interestingly, cancer patients receiving chemotherapeutic regiments containing cisplatinum appear to regain enhanced monocyte cytolytic activity both in vitro and in vivo. We postulated that cisplatinum may enhance the normal biological function of monocytes via its effect on IL-1 biology. Monocytes isolated from normal healthy subjects cultured in the presence of graded concentrations of cisplatinum with or without lipopolysaccharide (LPS) demonstrated significantly attenuated production of monocyte-derived IL-1ra in a dose-dependent manner. Moreover, the delayed addition of cisplatinum to monocyte cultures (up to 4 h), in relation to LPS stimulation, significantly suppressed IL-1ra protein by 49%. The level of this regulation was inhibition of IL-1ra mRNA. In contrast, cisplatinum failed to significantly inhibit the production of monocyte-derived IL-1 beta or other pro-inflammatory cytokines. These findings support the notion that cisplatinum has disparate effects on monocyte-derived cytokines, and provide a potential mechanism for cisplatinum's effects on monocyte function in cancer patients.

Base Sequence↗
PubMed1995

Chemokines and their role in human disease.

The recruitment of leukocyte populations to an area of inflammation is one of the most fundamental processes of immune reactivity, yet a number of the mechanisms which are important to this process are not clearly understood. Investigations directed at understanding the mechanisms of leukocyte elicitation have centered around classical chemotactic factors such as C5a and fMLP, however, these known agents have demonstrated little specificity for recruiting particular leukocyte populations. Recent advances in this field have been made with the discovery of a novel supergene family of chemotactic cytokines or chemokines. These cytokines are important as they possess a high degree of specificity for the recruitment of specific subpopulations of leukocytes.

Adult↗
PubMed1995

Production and function of monocyte chemoattractant protein-1 and other beta-chemokines in murine glial cells.

Monocyte chemoattractant protein-1 (MCP-1), formerly termed JE, is a member of the beta-chemokine (C-C chemokine) family and has been shown to be produced by a variety of cell types. Recently, mRNA of JE/MCP-1 was detected in astrocytes during the acute phase of experimental allergic encephalomyelitis (EAE). In addition, supernatants collected from human cultured astrocytes have recently been found to be chemotactic for monocytes. However, chemokine production and function in glial cells has not been fully examined. Using a sandwich ELISA assay, we have now quantitated MCP-1 levels and assessed MCP-1 function on murine glial cells. Lipopolysaccharide (LPS), interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha induced MCP-1 secretion by astrocytes, but not microglia. In addition, pretreatment with interferon (IFN)-gamma significantly augmented MCP-1 production by either LPS or the above cytokines. In contrast, LPS preferentially induced production of another beta-chemokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha) from microglial cells. MCP-1 induced chemotaxis of microglial cells and macrophages. Similarly, another beta-chemokine, TCA3, which is produced by encephalitogenic T lymphocytes, also induced chemotaxis of microglia and macrophages. These findings suggested that astrocytes and microglial cells differentially produce chemokines in the central nervous system, and that both astrocytes and T cells may facilitate recruitment and activation of microglial cells via production of beta-chemokines.

Animals↗
PubMed1995

Expression and biology of neutrophil and endothelial cell-derived chemokines.

The elicitation of polymorphonuclear leukocytes or neutrophils to an area of tissue injury is one of the most fundamental of all cell responses during the initiation of host defense. Historically, the neutrophil has been identified as an important phagocytic cell with a limited capacity to synthesize de-novo proteins. However, recent investigations have now shown that stimulated neutrophils can express a variety of cytokines, such as tumor necrosis factor, interleukin-1, interferon-alpha and interleukin-8. The ability of neutrophils and endothelial cells to produce interleukin-8 is extremely important, as this chemokine can contribute to the continued maintenance of cell infiltrates into the developing inflammatory lesion.

Base Sequence↗
PubMed1995

The role of CXC chemokines as regulators of angiogenesis.

The regulation of angiogenesis is fundamental to a variety of physiological and pathological processes. Although a number of factors have been identified that induce neovascularization, it is becoming increasingly apparent that endogenous angiostatic factors may play an important role in the regulation of angiogenesis during wound repair, chronic inflammation, and growth of solid tumors. In this review, we demonstrate that the CXC chemokine family of cytokines display disparate angiogenic activity depending upon the presence or absence of the ELR motif, a structural amino acid motif previously found to be important in receptor ligand binding on neutrophils. CXC chemokines containing the ELR motif are potent angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines that lack the ELR motif, PF4, IP-10, and MIG, not only fail to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovascularization, but are found to be potent angiostatic factors in the presence of CXC chemokines containing the ELR motif. These findings suggest that the CXC chemokine family can display disparate angiogenic activity that depends upon the presence or absence of the ELR motif. Furthermore, these studies support the notion that the net biological balance in the magnitude of expression of angiogenic and angiostatic CXC chemokines at either the site of wound repair or during tumorigenesis may be important in the regulation of net angiogenesis.

Animals↗
PubMed1995

Cardiac myocytes release leukocyte-stimulating factors.

The production of cytokines directly from cardiac myocytes has not been previously demonstrated and could represent an important mechanism and site of intervention in ischemia and reperfusion injuries. Macrophage inflammatory protein-2 (MIP-2) and monocyte chemotactic protein (MCP) are chemotactic cytokines (chemokines) that stimulate polymorphonuclear leukocytes (PMNs) and monocytes, respectively. Endothelium has been implicated as being a major cellular source of leukocyte-activating factors. We hypothesized that the myocardial cells may also play an important role in producing chemokines independently of endothelium. Primary cultures of adult rat ventricular myocytes were prepared. Cultured myocytes were stimulated with either interleukin 1 (IL-1), tumor necrosis factor (TNF), or lipopolysaccharide (LPS). MIP-2 and MCP mRNA were expressed in adult rat myocytes following stimulation. Our studies indicate that ventricular myocytes expressed chemokine mRNA and protein in both a dose- and time-dependent fashion. MIP-2 and MCP release, determined by enzyme-linked immunosorbent assay, was biologically active, accounting for approximately 40% of the PMN and monocyte chemotactic activity produced by these cells. These results suggest that cardiac myocytes may directly recruit activated leukocytes into areas of injury. Such a recruiting process could underlie the migration of leukocytes into areas of oxidant stress and play a role in development of reperfusion injury of myocardium.

Animals↗
PubMed1995

Stimulus and cell-specific expression of C-X-C and C-C chemokines by pulmonary stromal cell populations.

Chronic inflammatory responses in the lung rely on the continual recruitment of leukocytes to the site of inflammation. Recent data have demonstrated a possible role for stromal cell-derived chemokines in leukocyte recruitment. In the present study we examined the production of interleukin (IL)-8 and ENA-78, members of the C-X-C family of chemokines, and macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, members of the C-C chemokine family, from pulmonary smooth muscle and endothelial cells. The production of IL-8 and ENA-78 was induced by early response cytokines, IL-1 and tumor necrosis factor (TNF), but not by immune-associated cytokines, IL-4, IL-10, or interferon (IFN)-gamma. In contrast, the production of MIP-1 alpha and MIP-1 beta by pulmonary vascular smooth muscle cells increased when stimulated by immune-associated cytokines as well as with IL-1 beta and TNF. The level of MIP-1 alpha production induced in smooth muscle cells by the immune-associated cytokines, IL-4, IFN-gamma, and IL-10 ranged from 0 to 340 pg/ml. The production of MIP-1 beta in response to the immune-associated cytokines IL-4, IFN-gamma, and IL-10 in smooth muscle cells ranged from 260 to 940 pg/ml. Human pulmonary artery endothelial cells did not generate MIP-1 alpha or MIP-1 beta in response to graded doses of any of the cytokines. These data demonstrate differential induction of C-X-C and C-C chemokines from nonimmune stromal cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemokine CCL4↗
PubMed1995

Venous thrombosis-associated inflammation and attenuation with neutralizing antibodies to cytokines and adhesion molecules.

Thrombosis and inflammation are closely related. However, the response of the vein wall to venous thrombosis has been poorly documented. This study examines the hypothesis that venous thrombosis is associated with an inflammatory response in the vein wall. In a rat model of inferior vena caval thrombosis, vein wall was temporally examined for inflammation by assessment of histopathology, leukocyte morphometrics, and cytokine levels. Animals were killed 1 hour and 1, 3, and 6 days after thrombus induction. Our findings demonstrated an early (day 1) neutrophil infiltration into the vein wall followed by a later (days 3 and 6) monocyte/macrophage and lymphocyte response. Cytokines were elevated only under conditions of venous thrombosis. Levels of epithelial neutrophil activating protein-78 (ENA-78), tumor necrosis factor-alpha (TNF), interleukin-6, and JE/monocyte chemoattractant protein-1 (JE/MCP-1) increased over the 6-day period, while macrophage inflammatory protein-1 alpha (MIP-1 alpha) peaked at day 3 after thrombus induction. Additionally, rats were passively immunized with neutralizing antibodies to TNF, ENA-78, MIP-1 alpha, JE/MCP-1, intercellular adhesion molecule-1 (ICAM-1), and CD18 compared with control antibodies. The most effective antibody early after thrombus induction for attenuating vein wall neutrophil extravasation was anti-TNF (P < .01). The monocyte/macrophage extravasation was inhibited most by anti-ICAM-1 followed by anti-TNF (P < .01). These findings demonstrate that venous thrombosis is associated with significant vein wall inflammation that is partially inhibited by neutralizing antibodies to cytokines and adhesion molecules.

Animals↗
PubMed1995

Pleural mesothelial cell expression of C-C (monocyte chemotactic peptide) and C-X-C (interleukin 8) chemokines.

The arrival of inflammatory phagocytic cells, namely neutrophils and mononuclear phagocytes, in the pleural space is a hallmark of pleural inflammation. It is probable that the temporal arrival of cells is mediated via the release of chemotactic cytokines by activated mesothelial cells. We hypothesized that human pleural mesothelial cells activated by bacterial endotoxin lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), or tumor necrosis factor-alpha (TNF-alpha) release cell-specific chemokines from the C-C and C-X-C family of chemokines, specifically monocyte chemoattractant protein 1 (MCP-1) and IL-8. We evaluated supernatants of stimulated mesothelial cells for biologic chemotactic activity for monocytes and neutrophils and quantitative antigenic protein levels for MCP-1 and IL-8. Expression of the proteins at mRNA level was tested via Northern blot analysis. We found that responses to LPS were significantly higher (P less than 0.05) than control supernatants of unstimulated mesothelial cells. Responses to IL-1 beta and TNF-alpha were significantly greater than those to LPS. Neutralization studies with specific rabbit anti-MCP-1 and IL-1 antibody demonstrated significant decreases in bioactivity for MCP-1 and IL-8, indicating that mesothelial cell-derived MCP-1 and IL-8 play a significant role in the chemotactic activity seen in stimulated mesothelial cell supernatants. On specific enzyme-linked immunosorbent assay testing, stimulated mesothelial cells produced significantly more MCP-1 and IL-8 when stimulated with IL-1 beta or TNF-alpha as compared to LPS. mRNA expression for MCP-1 peaked within 2 to 4 h following stimulation and was noted as early as 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1995

Leukocyte infiltration in allergic airway inflammation.

The pathologic manifestation of an allergic airway response is a culmination of several coordinated events involving the participation of multiple mechanisms and cell types. The early release of mast cell-derived arachidonic acid metabolites, production of early-response cytokines, and increased expression of adhesion molecules and production of chemokines all lead to the recruitment of multiple cell types with the ability to participate in the allergic airway response. The coordinated use of animal models related to clinical observations will allow further elucidation of the mechanisms involved in the initiation, maintenance, and regulation of allergic airway inflammation leading to airway damage.

Cell Adhesion Molecules↗
PubMed1995

Alterations of ambient oxygen tension modulate the expression of tumor necrosis factor and macrophage inflammatory protein-1 alpha from murine alveolar macrophages.

Tissue injury that occurs as a result of ischemia and subsequent reperfusion is characterized by endothelial cell injury, edema formation, and the influx of inflammatory leukocytes. Two macrophage-derived proinflammatory cytokines which may play a critical role in cellular injury and leukocyte recruitment/activation that occurs in the setting of ischemia-reperfusion injury are tumor necrosis factor alpha (TNF) and macrophage inflammatory protein-1 alpha (MIP-1 alpha). To determine if modulation of ambient oxygen tensions in vitro alters the expression of proinflammatory cytokines from activated macrophages, murine alveolar macrophages (AMO) were cultured in various combinations of ambient oxygen concentrations, then the supernatant fluid and cell pellet assayed for the presence of TNF and MIP-1 alpha messenger RNA (mRNA) and protein. We demonstrated that conditions of anoxia (95% nitrogen/5% CO2) or hyperoxia (95% oxygen/5% CO2) independently resulted in the increased expression of both TNF and MIP-1 alpha mRNA and protein from lipopolysaccharide (LPS)-stimulated AMO, as compared with cells cultured in room air. The specific culture condition of anoxia (x 6 h) followed by hyperoxia (x 18 h) produced the greatest increases in both TNF and MIP-1 alpha, suggesting that when following a period of anoxic priming, oxygen stress results in exaggerated cytokine production. A period of at least 4.5 to 6 h of anoxia prior to hyperoxic exposure was found to be the minimal time required for anoxic priming. Furthermore, the coincubation of LPS-treated AMO with dimethyl sulfoxide (DMSO) attenuated the anoxia-hyperoxia-induced increases in TNF and MIP-1 alpha mRNA by 23% and 34%, respectively. These findings suggested that alterations in ambient oxygen tension can regulate the expression of TNF and MIP-1 alpha from activated AMO, and that oxidant-related cytokine production may represent an important mechanism by which inflammation occurs in the clinical settings of ischemia-reperfusion injury and hyperoxia.

Animals↗
PubMed1995

Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein.

The liver is highly susceptible to a number of pathological insults, including ischemia/reperfusion injury. One of the striking consequences of liver injury is the associated pulmonary dysfunction that may be related to the release of hepatic-derived cytokines. We have previously employed an animal model of hepatic ischemia/reperfusion injury, and demonstrated that this injury causes the production and release of hepatic-derived TNF, which mediates a neutrophil-dependent pulmonary microvascular injury. In this study, we have extended these previous observations to assess whether an interrelationship between TNF and the neutrophil chemoattractant/activating factor, epithelial neutrophil activating protein-78 (ENA-78), exists that may be accountable for the pathology of lung injury found in this model. In the context of hepatic ischemia/reperfusion injury, we demonstrated the following alterations in lung pathophysiology: (a) an increase in pulmonary microvascular permeability, lung neutrophil sequestration, and production of pulmonary-derived ENA-78; (b) passive immunization with neutralizing TNF antiserum resulted in a significant suppression of pulmonary-derived ENA-78; and (c) passive immunization with neutralizing ENA-78 antiserum resulted in a significant attenuation of pulmonary neutrophil sequestration and microvascular permeability similar to our previous studies with anti-TNF. These findings support the notion that pulmonary ENA-78 produced in response to hepatic-derived TNF is an important mediator of lung injury.

Animals↗
PubMed1995

Cultured lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis have a diminished capacity to synthesize prostaglandin E2 and to express cyclooxygenase-2.

Prostaglandin E2 (PGE2) inhibits fibroblast proliferation and collagen synthesis. In this study, we compared lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (F-IPF) and from patients undergoing resectional surgery for lung cancer (F-nl) with respect to their capacity for PGE2 synthesis and their expression and regulation of cyclooxygenase (COX) proteins. Basal COX activity, assessed by quantitating immunoreactive PGE2 synthesized from arachidonic acid, was twofold less (P < 0.05) in F-IPF than F-nl. In F-nl, incubation with the agonists PMA, LPS, or IL-1 increased COX activity and protein expression of the inducible form of COX, COX-2, and these responses were inhibited by coincubation with dexamethasone. By contrast, F-IPF failed to demonstrate increases in COX-2 protein expression or COX activity in response to these agonists. Under conditions of maximal induction, COX activity in F-IPF was sixfold less than that in F-nl (P < 0.05). Our data indicate that F-IPF have a striking defect in their capacity to synthesize the antiinflammatory and antifibrogenic molecule PGE2, apparently because of a diminished induction of COX-2 protein. This reduction in the endogenous capacity of F-IPF to down-regulate their function via PGE2 may contribute to the inflammatory and fibrogenic response in IPF. Moreover, we believe that this represents the first description of a defect in COX-2 expression in association with a human disease.

Base Sequence↗
PubMed1995

Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis.

In the enclosed study we have examined the expression and contribution of specific chemokines, macrophage inflammatory protein 1 alpha (MIP-1 alpha) and macrophage inflammatory protein 2 (MIP-2), and interleukin 10 (IL-10) during the evolution of type II collagen-induced arthritis (CIA). Detectable levels of chemotactic cytokine protein for MIP-1 alpha and MIP-2 were first observed between days 32 and 36, after initial type II collagen challenge, while increases in IL-10 were found between days 36 and 44. CIA mice passively immunized with antibodies directed against either MIP-1 alpha or MIP-2 demonstrated a delay in the onset of arthritis and a reduction of the severity of arthritis. On the contrary, CIA mice receiving neutralizing anti-IL-10 antibodies demonstrated an acceleration of the onset and an increase in the severity of arthritis. Interestingly, anti-IL-10 treatment increased the expression of MIP-1 alpha and MIP-2, as well as increased myeloperoxidase (MPO) activity and leukocyte infiltration in the inflamed joints. These data suggest that MIP-1 alpha and MIP-2 play a crucial role in the initiation and maintenance, while IL-10 appears to play a regulatory role during the development of experimental arthritis.

Animals↗
PubMed1995

Cytokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy.

We determined whether interleukin-8, monocyte chemotactic protein-1, and macrophage-colony stimulating factor are present in the vitreous of patients with proliferative diabetic retinopathy (PDR) or proliferative vitreoretinopathy (PVR). The levels of these cytokines were measured by specific enzyme-linked immunoassays in vitreous from 30 patients with PDR, 13 patients with PVR, and 26 control individuals, including 10 cadaver eyes and 16 patients with idiopathic macular holes, idiopathic macular puckers, vitreous hemorrhages, or uncomplicated retinal detachments. Detectable levels of interleukin-8 were found in 90% of vitreous samples of patients with PDR, 85% with PVR, and 58% of control samples. IL-8 was significantly increased in PDR (mean +/- SEM; 25.0 +/- 5.3 ng/ml; p = 0.01), but not in PVR (11.9 +/- 3.9 ng/ml; p = 0.50) compared to control human vitreous (8.5 +/- 2.5 2.5 ng/ml). MCP-1 was detected in 90% of vitreous samples of patients with PDR, 92% with PVR, and 81% of control samples. MCP-1 was significantly increased in PDR (6.2 +/- 0.9 ng/ml, p = 0.001) and PVR (7.7 +/- 2.5 ng/ml, p = 0.001) over the levels in control vitreous (1.2 +/- 0.2 ng/ml). M-CSF was detected in 94% of vitreous samples of patients with PDR, 88% with PVR, and 92% from control vitreous. M-CSF was significantly elevated in PDR (32.3 +/- 8.3 ng/ml, p = 0.03), but not in PVR (23.6 +/- 12.8 ng/ml, p = 0.4) compared to control (10.7 +/- 3.5 ng/ml). Our results suggest that IL-8, MCP-1, and M-CSF participate in the pathogenesis of PDR and PVR.

Chemokine CCL2↗