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Biomedical subjects

H Gewurz

Publications and source records attributed to H Gewurz.

At least 91 records · Page 5Linked to original sources
PubMed1982

A role for C-reactive protein in the complement-mediated stimulation of human neutrophils by type 27 Streptococcus pneumoniae.

Although C-reactive protein (CRP) has been shown to be opsonic when bound to erythrocytes, its role in bacterial phagocytosis is unclear. Chemiluminescence (CL), a measure of the metabolic stimulation of neutrophils, was used to investigate the effects of CRP and complement (C) on the interaction between phagocytes and Streptococcus pneumoniae, type 27 (Pn27). CRP binding to Pn27 was demonstrated by using radiolabeled CRP, and Scatchard analysis indicated a saturation binding of about 10(7) CRP molecules/CFU. When Pn27 was pretreated with normal human serum and added to neutrophils, the CL response observed was directly related to the number of bacteria and the amount of serum added. Although bacteria pretreated with CRP alone produced minimal CL, the addition of CRP to serum resulted in a two to 13-fold enhancement of the CL response. CRP enhancement of CL was not observed with heated serum or serum from a patient genetically lacking C2. CRP bound to Pn27 was found to cause consumption of C3 and C4 in normal human serum, indicating activation of the classical C pathway. Because CRP opsonization might provide early protection in the nonimmune host, we tested the ability of CRP to enhance opsonization in serum with markedly decreased immunoglobulin. CRP enhanced the CL response in serum from a hypogammaglobulinemic patient to between 12 and 16 times the serum control. These studies show CRP binds to Pn27 and in the presence of C enhances the opsonization of these organisms. These findings support the concept that CRP plays a protective role in bacterial infection.

Agammaglobulinemia↗
PubMed1982

Comparison of the enzymatic sensitivities of the platelet receptor for human C-reactive protein and its functional relationship to the platelet IgG Fc receptor.

Thermally modified human C-reactive protein (H-CRP) and IgG (AHGG) each activate isolated human platelets to reactions of aggregation and secretion. As these molecules exhibit many functional similarities, we questioned whether they might also share a receptor on the platelet membrane. Neither plasmin nor phospholipase C altered the platelet response to H-CRP or AHGG, although these reagents enhanced the platelet expression to acid soluble collagen (ASC). Conversely, chymotrypsin treatment of platelets resulted in an elevated response to each H-CRP and AHGG, but not to ASC. These data suggest that the H-CRP and AHGG platelet receptors share characteristics which contrast with those of the receptor for collagen. However, monomeric IgG, which can bind with the platelet and inhibit the response to AHGG, exerted no effect on the platelet response to H-CRP. Further, a functional receptor for thermally modified human or rabbit CRP was detected on rabbit platelets in the absence of a demonstrable Fc receptor for aggregated IgG. These data indicate that the platelet receptors for the modified forms of CRP and IgG are distinct.

Animals↗
PubMed1981

C-reactive protein is protective against Streptococcus pneumoniae infection in mice.

C-reactive protein (CRP) has several properties that suggest that it may function as a bacterial opsonin. CRP shows binding reactivity with pneumococcal C-polysaccharide, the cell wall carbohydrate of Streptococcus pneumoniae. In this study we have demonstrated protection of mice against serotypes 3 and 4 of S. pneumoniae infection by a single prior injection of CRP. This effect was seen both in mice that lacked antibody to phosphocholine and in normal mice. Thus the opsonic properties of CRP previously described may be related to protection against pneumococcal infection.

Animals↗
PubMed1981

Inhibitory effect of C-reactive protein on alternative C pathway activation by liposomes and Streptococcus pneumoniae.

C-reactive protein (CRP) is an acute phase serum protein found associated with damaged tissue at sites of inflammation. CRP bound to multivalent phosphocholine-containing or polycationic ligands activates C by the classical pathway. We have previously described liposomes of a particular lipid composition that are able both to activate the alternative pathway of C and to bind CRP. In addition many strains of Streptococcus pneumoniae activate the alternative pathway. We have shown CRP binding to these bacteria as well. Because antibody to an activating surface in many cases enhances alternative pathway activation, we tested CRP for a similar function in these systems. Our results indicate that, in contrast to antibody, CRP inhibits alternative pathway activation. This inhibition by CRP is apparently restricted to surfaces that bind CRP. Thus, CRP binding to membrane or bacterial surfaces can convert them from alternative pathway activation to classical pathway activation.

Amines↗
PubMed1981

Localization of C-reactive protein in inflammatory lesions of experimental allergic encephalomyelitis.

C-reactive protein (CRP) is an acute-phase reactant which has been found deposited at sites of inflammation and tissue destruction. Experimental allergic encephalomyelitis (EAE) is a demyelinating disease of the central nervous system characterized by inflammatory cellular infiltrates. This study describes the CRP response and the deposition of CRP in the spinal cords of rabbits with EAE. EAE was induced by a single injection of rabbit spinal cord in Freund's complete adjuvant. Serum CRP levels in experimental and adjuvant control rabbits showed cyclic elevations. An additional increase in levels of CRP in the serum was observed in the experimental group coincident with the onset of clinical disease. Deposition of CRP in spinal cord lesions of six of nine animals with EAE was demonstrated by direct immunofluorescence. CRP was seen around and within a small proportion of the cells in the acute inflammatory lesion. The amount of CRP deposition was most closely correlated with the proportion of polymorphonuclear leucocytes (PMN) in the infiltrate. No staining was observed in control animals, in experimental animals prior to the onset of clinical signs of EAE, or in clinically affected animals with exclusively mononuclear infiltration. The demonstration of CRP and PMN in acute lesions of rabbits with EAE may reflect a role for humoral mediators of inflammation in this disease.

Animals↗
PubMed1981

Binding of C-reactive protein to human lymphocytes. I. Requirement for a binding specificity.

Our laboratory previously reported that C-reactive protein (CRP) binds selectively to T lymphocytes and inhibits certain of their reactivities in vitro. However, these findings could not be repeated using more highly purified CRP preparations even under a variety of experimental conditions. Purified CRP alone did not bind to peripheral blood lymphocytes (PBL); however, in the presence of a ligand such as pneumococcal C-polysaccharide (CPS), CRP binding was readily detectable both by immunofluorescence and by a radioassay established for this purpose. The optimal concentration of CRP, ratio of CRP:CPS, and time and temperature for reactivity were determined using both assays. A markedly enhanced rate of binding was observed after pre-equilibration of CRP with calcium. A small percentage (mean 3.0%; range 0.5 to 8.0%) of PBL bound complexed CRP, and saturation was reached with 200 microgram CRP/ml. Reactivity of CRP with a multimeric form of phosphocholine (PC) (KLH-PC44) led to binding comparable to that observed with CPS, whereas monomeric PC inhibited the binding. Thus, in the presence of a multimeric binding specificity, CRP binds to a small fraction of peripheral blood lymphocytes, which are characterized in the accompanying paper.

Binding Sites↗
PubMed1981

Binding of C-reactive protein to human lymphocytes. II. Interaction with a subset of cells bearing the Fc receptor.

In the preceding paper we reported that C-reactive protein (CRP) in the presence of a multimeric binding specificity such as C-polysaccharide (CPS) binds to a small percentage of peripheral blood lymphocytes (PBL). In the present paper additional methods for demonstrating this binding were developed and utilized to help characterize the CRP-binding cell. Heat-modified CRP and E-CPS-CRP each were found to bind to a similar percentage of PBL by microscopic visualization, and an identical degree of binding was observed by cytofluorimetric analysis. Multiple marker studies indicated that CRP-binding cells are found in the T cell, B cell, and null cell categories in a ratio of 2:1:1, respectively. Preferential overlap was seen with IgG FcR-bearing cells, which accounted for 70% of the CRP-binding cells; however, only 12% of the FcR cells bound CRP. These studies indicate that CRP-binding cells predominantly represent a subset of cells bearing FcR, and these cells have the morphologic characteristics of large granular lymphocytes. CRP in the presence of CPS bound to cells of multiple human and murine cultured lines shown to have IgG FcR reactivity, but showed lesser or no binding to cell lines negative for FcR. The precise morphologic and functional characterization of the CRP-binding cells and the nature of the binding site are yet to be established.

Binding Sites↗
PubMed1981

Renal transplantation in a patient with hereditary deficiency of the second component of complement.

The HLA haplotype A 10,B18 has been associated with hereditary deficiency of the second component of complement(C2). In an effort to detect individuals homozygous for C2 deficiency, a thorough audit of HLA serotyping results in 3,100 individuals was performed, and a single patient homozygous for the A10, B18 haplotype was identified. Detailed complement studies in this patient's serum and plasma revealed previously undetected selective absence of C2 antigen and haemolytic activity, and a hereditary basis for this deficiency was indicated by half-normal levels of C2 haemolytic activity in both of his children. The patient was of special interest in that he had previously developed renal failure which was treated by cadaver kidney transplantation. C2 antigen was undetectable in serum and plasma samples taken prior to and up to 9 months following transplantation. This experience suggests that HLA serotyping can be a valuable screening technique for the detection of individuals with C2 deficiency, and that renal transplantation does not reconstitute normal levels of C2.

Adult↗
PubMed1981

Binding reactivity of C-reactive protein for polycations. II. Modulatory effects of calcium and phosphocholine.

C-reactive protein previously was shown to selectively and reversibly precipitate with certain small polymers of arginine and lysine. In the present report, calcium was shown to inhibit this reactivity in a dose-dependent manner, in direct contrast to the requirement for calcium for precipitation of CRP with C-polysaccharide. However, in the presence of phosphocholine, CRP rapidly precipitated and formed stable complexes with the polycationic polymers in the otherwise inhibitory calcium concentrations. alpha-Glycerol-phosphocholine, unlike phosphocholine, did not reverse this inhibitory effect. These results extend the characterization of the binding reactivity of CRP for polycations and suggest a relationship between this binding site and the sites for calcium and phosphocholine. We propose that CRP-polycation interactions in the presence of phosphocholine may have physiologic significance during the acute inflammatory process.

Binding Sites↗
PubMed1981

Agglutination of complement-coated erythrocytes by serum amyloid P-component.

Serum amyloid P-component (SAP) is a normal plasma glycoprotein apparently identical with the P-component associated with amyloid deposits. SAP shows extensive amino acid sequence homology with the C-reactive protein, and both have a similar molecular configuration. SAP undergoes calcium-dependent binding to zymosan, agarose, and amyloid fibrils, but its functional properties are not yet known. We report here that SAP agglutinates complement-(C) coated antibody-sensitized erythrocytes by a calcium-dependent reaction. SAP was found to interact predominantly with a modified form of bound C3b. This modification was achieved by prolonged treatment of EAC43 with heated normal human serum or with isolated C3bINA and beta 1H, and reactivity was reduced upon treatment of the cells with trypsin. SAP thus seems to react with fixed C3 in a manner similar to the reaction of C3 with bovine conglutinin, a molecule that also undergoes calcium-dependent binding to zymosan and agarose. These studies identify a new reactivity for SAP and demonstrate an interaction between an amyloid protein and the C system. The close similarity between the calcium-dependent binding specificities of SAP and of bovine conglutinin may assist in characterization of these molecules and in investigation of their function.

Agglutination↗
PubMed1981

Interaction of C-reactive protein with liposomes. III. Membrane requirements for binding.

We have previously presented a model for CRP-membrane interactions using liposomes composed of dimyristoyl phosphatidylcholine (DMPC), cholesterol (CHOL), stearylamine (SA), and galactosyl ceramide. We have shown that the interaction of cRP with these liposomes in the presence of human serum results in consumption of hemolytic C and membrane lysis. In the present paper we have directly examined the binding reaction between CRP and liposomes using radiolabeled CRP. We have found that this binding is more characteristic of CRP interactions with polycations than CRP interactions with phosphocholine- (PC) containing molecules. CRP binding to liposomes was dependent on the presence of SA in the membrane and could occur with dimyristoyl phosphatidylethanolamine in place of DMPC. The binding was not inhibited by ethylenediaminetetraacetate (EDTA) but could be inhibited by CaCl2, whereas CRP binding to PC-Sepharose was inhibited by EDTA and required CaCl2. We have further examined the effects of changes in membrane composition on CRP binding to liposomes. In liposomes with a limiting density of SA, we found increased CRP binding with changes in composition that would increase membrane fluidity. In most cases, the amount of CRP binding correlated with the amount of C activation observed previously. However, increasing the amount of CHOL in the membrane was found to increase C activation while decreasing CRP binding. These findings indicate that CRP binding to membranes and subsequent C activation can occur through cationic molecules as well as phospholipids.

Amines↗
PubMed1980

A hypocomplementemic vasculitic urticarial syndrome. Report of four new cases and definition of the disease.

We describe four new patients with a unique syndrome of persistent urticaria, with leukoclastic angiitis, severe angioedema, occasional life-threatening laryngeal edema, arthritis, arthralgia, neurologic abnormalities and pronounced persistent hypocomplementemia. The complement abnormalities involved markedly reduced levels of the Clq subunit of the first component of complement (Cl) in the presence of near normal levels of Clr and Cls subunits of Cl; modest to marked depletion of the fourth component of complement (C4), the second component of complement (C2) and the third component of complement (C3); and normal levels of the fifth through ninth components of complement (C5 through C9) and properdin factors B and D. A striking serologic abnormality found in all patients was the presence of low molecular weight (7S) proteins which precipitated with Clq in agarose gels; these previously were shown to be comprised at least in part of immunoglobulin G. The present experience is offered to help to define the clinical, histopathologic and serologic characteristics of this entity, designated hypocomplementemic vasculitic urticarial syndrome, and to emphasize its distinctiveness and prevalence.

Adult↗