Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell-mediated immunity is clearly the critical host defense mechanism against human Coxiella burnetii infection (Q fever); the role of specific antibody is unclear. By using a mouse macrophage tumor cell line, J774, persistently infected with C. burnetii phase I organisms, in a standard 51Cr-release cytotoxicity assay, we explored the possibility that antibody-dependent cellular cytotoxicity may be immune mechanism in Q fever. After 16 h of incubation in the presence of immune sera from Q fever hepatitis or endocarditis patients, nonimmune human peripheral blood effector cells specifically lysed infected J774 target cells; no 51Cr release was seen in the presence of nonimmune sera or uninfected target cells. An effector/target ratio of at least 5:1 was required, and monocytes were more efficient effector cells than lymphocytes. Cytotoxicity was blocked by preincubation of effector cells with purified aggregated human immunoglobulin G, indicating the role of Fc receptor-bearing effector cells. Two nonphagocytic lymphoid tumor cell targets, passively coated with C. burnetii, did not induce substantial immune-specific cytolysis, suggesting that bystander lysis does not explain the observation of specific lysis. Although antibody-dependent cellular cytotoxicity may participate in primary defense, alternatively, it may facilitate the dissemination of C. burnetii or surreptitiously participate in granuloma formation.
 ...
PMID:Antibody-dependent cellular cytotoxicity of Coxiella burnetii-infected J774 macrophage target cells. 669 Apr 2

Staphylococcus aureus is a leading cause of infective endocarditis (IE). Platelet activation promoted by S. aureus resulting in aggregation and thrombus formation is an important step in the pathogenesis of IE. Here, we report that the fibrinogen/fibronectin-binding proteins FnBPA and FnBPB are major platelet-activating factors on the surface of S. aureus from the exponential phase of growth. Truncated derivatives of FnBPA, presenting either the fibrinogen-binding A domain or the fibronectin-binding BCD region, each promoted platelet activation when expressed on the surface of S. aureus or Lactococcus lactis, indicating two distinct mechanisms of activation. FnBPA-promoted platelet activation is mediated by fibrinogen and fibronectin bridges between the A domain and the BCD domains, respectively, to the low affinity form of the integrin GPIIb/IIIa on resting platelets. Antibodies recognizing the FnBPA A domain or the complex between the FnBPA BCD domains and fibronectin were essential for activation promoted by bacteria expressing the A domain or the BCD domain respectively. Activation was inhibited by a monoclonal antibody (IV-3) specific for the FcgammaRIIa IgG receptor on platelets. We propose that the activation of quiescent platelets by bacteria expressing FnBPs involves the formation of a bridge between the bacterial cell and the platelet surface by (i) fibronectin and fibrinogen interacting with the low affinity form of GPIIb/IIIa and (ii) by antibodies specific to FnBPs that engage the platelet Fc receptor FcgammaRIIa. Platelet activation by S. aureus clinical IE isolates from both the exponential and stationary phases of growth was completely inhibited by monoclonal antibody IV-3 suggesting that the IgG-FcgammaRIIa interaction is of fundamental importance for platelet activation mediated by this organism. This suggests new avenues for development of therapeutics against vascular infections.
 ...
PMID:Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the FcgammaRIIa receptor. 1635 30