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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alveolar macrophages (AMS) initiate inflammation during Pneumocystis carinii pneumonia by releasing cytokines including TNF-alpha. Recent studies suggest that macrophage responses to P. carinii are enhanced by serum opsonization, but the mechanisms of enhancement are not well defined. To determine whether macrophage release of TNF-alpha in response to P. carinii was augmented by immune opsonization, alveolar macrophages obtained from rabbits were cultured with P. carinii that had been opsonized with either nonimmune rabbit serum, immune serum generated against P. carinii, or an affinity-purified polyclonal Ab recognizing the major P. carinii surface Ag gp120. Each experiment also included organisms maintained in media alone (nonopsonized P. carinii). Opsonization of P. carinii with immune serum or gp120 Ab significantly enhanced macrophage TNF-alpha release. Interestingly, however, opsonization with nonimmune serum also increased TNF-alpha response to the organism. Because P. carinii is known to interact with the adhesive glycoproteins, vitronectin (VN) and fibronectin (FN), we hypothesized that they might also augment TNF-alpha release. Opsonization of P. carinii with VN or FN resulted in significant potentiation of macrophage TNF-alpha liberation. We further determined that VN and FN were present in increased quantities in the lower respiratory tract of patients with P. carinii pneumonia compared with normal volunteers. Additionally, VN and FN were demonstrated on the surface of freshly isolated P. carinii organisms by immunoblot analysis. Our study suggests that immune and nonimmune opsonins contribute to host defenses during P. carinii pneumonia by enhancing regional TNF-alpha release in response to the organism.
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PMID:Vitronectin, fibronectin, and gp120 antibody enhance macrophage release of TNF-alpha in response to Pneumocystis carinii. 751 99

An initial and crucial step in the establishment of many microbial infections is the attachment of the pathogen to the host cells. Thus, adherence of Pneumocystis carinii (Pc) to type I pneumocytes is believed to be important in the induction of Pc pneumonia. Little is known about the nature of the attachment of Pc to type I cells, although extracellular matrix (ECM) proteins, such as fibronectin and laminin, have been implicated in the process. We report here the isolation of a Pc gene encoding a receptor protein that binds both fibronectin and laminin in vitro. A cDNA clone encoding the Pc ECM receptor was isolated from a Pc cDNA library and identified on the basis of sequence homology to the human colon carcinoma laminin receptor. Southern blot analysis of Pc genomic DNA confirmed that the cDNA was of Pc origin. Northern blot analysis of Pc total RNA showed a predominant mRNA of approximately 1400 nucleotides that hybridized to the ECM receptor gene. The ECM receptor predicted from the cDNA sequence is 295 amino acid residues long, with a molecular mass of 32.8 kDa. The C-terminal third of the polypeptide is highly negatively charged, whereas the N-terminal two-thirds contains hydrophobic segments that may play a role in membrane association. Sequence analysis and alignment of the N terminus with the laminin receptor cDNA sequence of human colon carcinoma support the conclusion that the Pc ECM receptor cDNA clone is a full-length clone. A Western blot of the overexpressed ECM receptor protein bound both laminin and fibronectin in vitro. Antibodies raised to the overexpressed receptor protein interacted with a 33-kDa protein in total Pc cell lysates. These findings raise the possibility that the Pc ECM receptor protein may mediate the organism's attachment to type I pneumocytes and, thus, may play a crucial role in Pc pathogenesis.
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PMID:Gene for an extracellular matrix receptor protein from Pneumocystis carinii. 751 77

The organic symptoms and results of coagulation tests of disseminated intravascular coagulopathy (DIC) in 17 patients with infection were compared with those in 12 patients with malignancy. The infectious diseases were mainly sepsis and pneumonia, and the malignancy was mainly lung cancer. The mean antithrombin III (AT III) before treatment was 54% in infection and 68% in malignancy, and the AT III values improved after administration of 1500 U of AT III concentrates per day. The mean thrombin-antithrombin complex level decreased from 22 ng/ml to 9 ng/ml after the treatment in infection, but it increased in malignancy. There were no differences in DIC scores between infection and malignancy before treatment; however, the scores were significantly more improved in infection than in malignancy after treatment (p < 0.05). The fibrin/fibrinogen degradation product level, platelet count, and fibronectin level were also significantly more improved in infection than in malignancy. This better response to treatment in infection than in malignancy is probably due to eradication of the causative organisms by antibiotics in infection. These data suggest that therapy against both DIC and the underlying disease is crucial for successful treatment.
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PMID:Disseminated intravascular coagulopathy in infection compared with that in malignant neoplasia. 774 1

Group B streptococci (GBS) are the leading cause of neonatal pneumonia and meningitis. Adherence of GBS to host tissues may play an important role in the pathogenesis of infection. The host molecules which mediate GBS adherence to host tissues are unknown. Many bacterial pathogens adhere to fibronectin, an important component of the extracellular matrix (ECM). Some pathogens adhere to both immobilized and soluble fibronectin, while others adhere to immobilized fibronectin, but not to soluble fibronectin. Previous data indicated that GBS do not adhere to soluble fibronectin. We studied the ability of GBS to adhere to immobilized fibronectin. Forty-five per cent of the input inoculum of COH1, a virulent GBS isolate, adhered to fibronectin immobilized on polystyrene. COH1 did not adhere to the other ECM proteins tested (laminin, type I collagen, vitronectin, and tenascin). Nine out of nine GBS strains from human sources tested adhered specifically to fibronectin at levels varying from 4-60%. We considered the possibility that GBS were adherent to a contaminant in the fibronectin preparation. Properties of fibronectin, including the presence of an immunologic epitope of fibronectin and binding to collagen, were verified to be properties of the molecule to which GBS adhere. COH1 adhered to fibronectin captured by a monoclonal antibody to fibronectin (FN-15), confirming that the molecule to which GBS adhere bears immunologic determinants of fibronectin. Adherence of COH1 to fibronectin was inhibited by collagen, confirming that the molecule to which GBS adhere binds to collagen. These data strongly suggest that GBS adhere to fibronectin, and not to a contaminant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Group B streptococci adhere to a variant of fibronectin attached to a solid phase. 778 28

Staphylococcus aureus remains a prominent cause of community- and hospital-acquired infection. This study reviewed 162 cases of S. aureus infection occurring in 120 adults who were hospitalized at a Veterans Affairs Medical Center and referred for consultation to the Infectious Disease Service. There were 37 cases of skin and soft tissue infection, 5 pyomyositis, 34 osteomyelitis, 13 septic arthritis, 19 pneumonia, 3 empyema, 5 pyelonephritis, 37 vascular infection, 3 epidural abscess, and 6 miscellaneous infections. Bacteremia was documented in 56 of 119 (47%) cases in which blood cultures were obtained, indicating the serious nature of the infections in many cases. Staphylococcus aureus is widely prevalent in healthy persons. Given its ubiquity and the capacity to cause a broad array of infections, an effective host response must play an important role in preventing infection. This host response is immunologically nonspecific, in that it depends upon the effectiveness of mechanical barriers to invasion and, once invasion takes place, the interaction of PMN, complement, and antibody that is probably present in serum of all immunologically competent adults rather than sensitization of B or T lymphocytes by any identifiable antigens specific to S. aureus. Analysis of the present cases calls attention to S. aureus as an opportunistic pathogen, 1 that only infrequently causes serious infection in otherwise healthy persons. Nearly every patient in this series had 1 or more medical condition thought to predispose to infection; 279 such conditions were identified, representing an average of 2.3 per person. A break in the natural barrier to infection was also present in the majority of cases, for example, trauma, wound, or pre-existing decubitus ulcer in skin and soft tissue infections; endotracheal tube in pneumonia; and a catheter bypassing urethra or skin in urinary and vascular infections, respectively. The tendency for patients to be infected with S. aureus repeatedly (mean number of infections, 1.4 per patient) reflects the chronicity of many predisposing factors and, perhaps, of colonization as well. Staphylococcus aureus has a special predilection to cause infections involving prosthetic devices, perhaps related to its affinity for fibronectin, laminin, and other serum proteins that can mediate attachment to foreign material; 46 of 162 (28%) infections were associated with the presence of a foreign body. Such infections are difficult to eradicate with antibiotic therapy alone, perhaps because of a change in the metabolic state of adherent bacteria, and removal of the foreign body is generally required for cure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The current spectrum of Staphylococcus aureus infection in a tertiary care hospital. 804 Dec 42

The opsonic activity of plasma fibronectin (FN) by rat alveolar macrophage (AM) was examined, and the in vivo effect of FN in Staphylococcus aureus (S. aureus) experimental rat pneumonia was evaluated. The chemiluminescence response of AM was enhanced by the presence of FN (300 micrograms/ml) in S. aureus and Streptococcus pneumoniae, but was not enhanced in gram-negative rods (Haemophilus influenzae, Branhamella catarrhalis, Pseudomonas aeruginosa). FN (300 micrograms/ml) promoted the phagocytosis of S. aureus by AM, but did not promote the bactericidal activity of that by AM. In the experimental rat pneumonia with S. aureus inoculation, plasma FN concentration decreased with time, but increased by the administration of FN (1 mg). The number of bacteria in the lung, peripheral white blood cell and BAL fluid cell also decreased by the administration of FN. Furthermore, FN was significantly improved on inflammatory findings of rat lung tissue 24 hours after inoculation with S. aureus. These results suggest that FN plays an important role as an opsonic by alveolar macrophage, and that FN has utility for clinical trials in patients with pneumonia.
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PMID:[Efficacy of fibronectin on opsonic activity by alveolar macrophage and experimental rat pneumonia]. 833 12

The attachment of Pneumocystis carinii to lung cells could play a role in the pathophysiology of P carinii pneumonia. The trophozoite attaches to type I alveolar epithelial cells. Physical, chemical, and extracellular matrix factors, involved in the mouse-or rat-derived P carinii attachment to fibroblastic cells in culture, were examined using a new model of in vitro adherence. The development of parasite filopodia penetrating deeply the host cell cytoplasm was observed using transmission electronic microscopy. Killed P carinii organisms were unable to attach to cultured cells. Also, parasites were unable to attach to killed target cells. The P carinii in vitro attachment was partially inhibited by cytochalasin B. In contrast, the parasite attachment was not affected when the target cell cytoskeleton was altered. In our work conditions, sialic acids were not involved in the attachment process. Present results showed that fibronectin (Fn) plays a role in the parasite attachment, and suggest that a specific Fn-binding receptor is present at the surface of mouse-derived P carinii organisms.
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PMID:In vitro attachment of Pneumocystis carinii from mouse and rat origin. 836 1

Pneumocystis carinii (PC) is a leading cause of pneumonia in immunocompromised patients. Previous work has shown that fibronectin (Fn) and Fn-binding integrins mediate PC attachment to lung cells in vitro. Gamma-interferon (gamma-IFN) is a major factor in host defence against PC infection. To determine the effect of gamma-IFN on PC attachment to lung cells, the alveolar epithelial cell line A549 was incubated with gamma-IFN (0-10(4) U mL(-1)) and attachment of 51Cr-labelled PC to the A549 cells was quantified. PC attachment was significantly decreased (P < 0.01) by addition of gamma-IFN with no evidence of injury to either the PC or A549 cells. Effects of gamma-IFN on PC attachment were observed after 24 h and reached a maximum after 48 h of incubation. To investigate the mechanism of this decrease, we examined integrin expression on gamma-IFN-treated A549 cells. A549 cell expression of the alpha5 and beta1 integrin subunits was decreased, whereas expression of the alpha(v) subunit was unchanged. Northern blot analysis showed a similar decrease in mRNA for the alpha5 and beta1 integrins. Therefore, gamma-IFN-mediated inhibition of PC infection may, in part, result from inhibition of PC attachment to alveolar epithelial cells caused by gamma-IFN-induced decreases in alveolar integrin expression.
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PMID:Gamma-interferon inhibits Pneumocystis carinii attachment to lung cells by decreasing expression of lung cell-surface integrins. 904 72

Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 +/- 3 years (mean +/- SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1 beta and IL-6 were found to be 15-fold higher on admission (122 +/- 9 pg mL-1 and 60 +/- 4 pg mL-1 respectively), whereas TNF-alpha was three-fold higher (102 +/- 5 pg mL-1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 +/- 1 mg L-1), whereas fibronectin levels were reduced (242 +/- 9 mg dL-1). The presence of parapneumonic effusion was associated with a higher TNF-alpha serum level (127 +/- 7 vs. 86 +/- 4 pg mL-1, P = 0.0002), a more rapid daily decline in TNF-alpha (-7.2 +/- 0.7 vs. -3.8 +/- 0.5 pg mL-1 day-1, P = 0.0005), a slower rate of decline in CRP (-42.8 +/- 3.0 vs. -54.6 +/- 3.0 mg L-1 day-1, P = 0.02) and a slower rate of increase in FBN (5.9 +/- 1.0 vs. 11.7 +/- 1.0 mg dL-1 day-1), P = 0.001]. Furthermore, daily progression of serum levels of cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar-arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition.
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PMID:Daily variation in circulating cytokines and acute-phase proteins correlates with clinical and laboratory indices in community-acquired pneumonia. 913 79

Pneumocystis carinii pneumonia remains a serious complication of immunodeficiency. Vitronectin (VN) and fibronectin (FN) accumulate in the lung during P. carinii infection and bind to the organism, thereby enhancing macrophage release of TNF alpha. It is not known whether VN and FN also regulate uptake and degradation of P. carinii by macrophage when present in concentrations similar to those in the lung during pneumonia. To address this, macrophages were cultured with 35S-radiolabeled P. carinii and organism binding, phagocytosis, and degradation determined in media alone (control), or in the presence of VN or FN (100 micrograms/ml each). Soluble VN and FN, in concentrations similar to those in the host, did not significantly affect binding uptake or degradation of P. carinii by alveolar macrophages. Thus, although VN and FN enhance macrophage activation during P. carinii pneumonia, phagocytosis of the organism is not increased by these host glycoproteins under steady-state conditions.
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PMID:Steady-state effects of vitronectin and fibronectin on the binding, uptake, and degradation of Pneumocystis carinii in rat alveolar macrophages. 924 75


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