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Biomedical subjects

M J Polley

Publications and source records attributed to M J Polley.

14 recordsLinked to original sources
PubMed1992

Neutrophil-dependent acute lung injury. Requirement for P-selectin (GMP-140).

Rapid translocation of P-selectin (GMP-140) from cytoplasmic granules to the cell membrane of endothelial cells promotes adhesive interactions with neutrophils which, when activated, damage the endothelium. The role of P-selectin in lung vascular endothelial injury in rats after systemic activation of complement by intravenous infusion of cobra venom factor has been assessed. Within 5-10 min after cobra venom factor infusion, the pulmonary vasculature demonstrated immunohistochemical expression of an epitope that reacts with anti-human P-selectin. Monoclonal antibody to human P-selectin blocked in vitro adherence of rat or human platelets (activated with thrombin) to neutrophils and was demonstrated to react with thrombin-activated rat platelets. The antibody did not react with rat neutrophils. In vivo, the antibody had strongly protective effects against cobra venom factor-induced pulmonary vascular injury as determined by permeability changes and hemorrhage. In parallel, lung myeloperoxidase content was greatly reduced and, by transmission electron microscopy, there was markedly diminished adherence of neutrophils to the pulmonary vascular endothelium and much diminished injury of endothelial cells, as defined by hemorrhage. These data indicate that anti-human P-selectin reacts with a pulmonary vascular antigen in rats and that this antigen is essential for the full expression of lung injury.

Acute Disease↗
PubMed1991

CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x.

The leukocyte receptor CD62, which is expressed on activated platelets and endothelial cells, is shown to mediate cell adhesion by binding a sialylated carbohydrate structure, sialyl-Lewis x, found on neutrophils, monocytes, and tumor cells. This structure has previously been identified as the ligand for another member of the LEC-CAM family of cell adhesion molecules, endothelial cell-leukocyte adhesion molecule 1, which also binds neutrophils and monocytes. The results demonstrate that although the two LEC-CAMs differ in their biological activities by their distribution and mode of expression, they are capable of mediating cell adhesion by recognition of the same carbohydrate ligand.

Animals↗
PubMed1979

Human complement in thrombin-mediated platelet function: uptake of the C5b-9 complex.

Thrombin-mediated platelet aggregation and release is enhanced by the presence of C3, C5, C6, C7, C8, and C9 of human complement. The interaction of thrombin with its receptor on the platelet membrane initiates activation of complement on the platelet surface. Trypsin-mediated platelet function is not enhanced by the addition of complement, probably because trypsin has no receptor on the platelet surface so activation of complement is triggered in the fluid phase and not on the platelet surface. Activation of complement by thrombin led to production of dimers of the C5b-9 complex on the platelet surface. These complexes were eluted from the platelet membrane and were identified physicochemically and morphologically. The mechanism of complement-induced enhancement of platelet function is not clear, however, it probably is mediated via the arachidonic acid transormation pathway because this activity was blocked by known inhibitors of cyclo-oxygenase, namely, aspirin and indomethacin.

Antithrombin III↗
PubMed1979

Action of complement in the lysis of mouse sarcoma cells sensitized with H-2 alloantibody.

A modified cytotoxicity assay was adapted from classical erythrocytolytic assays, in which complement components were added in sequence to antibody-sensitized cells. This assay was applied to a model system in which mouse sarcoma cells were sensitized with H-2 alloantibody. The stepwise presentation of complement components combined with the stabilization of C2 by iodine treatment considerably augmented the lytic efficiency of human complement. More generally, the techniques adopted for this study provide a new model for obtaining basic information about selective reaction steps concerned in lysis of nucleated cells by alloantibody and complement. Comparisons of the lysis of sheep erythrocytes by xenoantibody with the lysis of mouse sarcoma cells by H-2 alloantibody, in our assay system with oxidized or untreated human complement, disclosed a difference in the kinetics of C142 formation, manifest in a lag phase and a protracted tmax for the sarcoma cells. These data may suggest that multiple complement-mediated functional lesions are necessary for immune lysis of nucleated cells.

Animals↗
PubMed1978

The human complement system in thrombin-mediated platelet function.

Thrombin-mediated platelet membrane-specific uptake of C3 and C5 was demonstrated by radiolabeled components and was visualized electron microscopically utilizing a ferritin marker conjugated to monospecific antibody to each component. The role of complement in thrombin-induced platelet function was determined. Though complement was not essential for thrombin-induced platelet aggregation and release of serotonin, these activities were significantly increased if complement was present. The release of serotonin was found to be a nonlytic process because under the conditions employed, no lactic dehydrogenase was released. The activation of complement was induced by a mechanism which has not been previously described. Thrombin associated with the platelet membrane presumably formed a C3 convertase that entered the known complement sequence at the C3 stage and proceeded to activate the terminal components through the known sequence to C9.

Blood Platelets↗
PubMed1978

Membrane receptors of mouse leukocytes. I. Two types of complement receptors for different regions of C3.

Mouse leukocytes were studied for membrane receptors for the third C component by rosette formation with C coated erythrocytes (EAC). Methods were devised for the preparation of EAC complexes containing either mouse C3b or mouse C3d. EAC 1-3dmo were prepared from EA treated with whole mouse serum while EAC 1-3bmo were produced from EAC 142hu treated with whole mouse serum containing sodium suramin. The specificity of the EAC complexes for mouse leukocytes was confirmed by inhibition experiments using fluid phase human C3d. Low concentrations of fluid phase human C3d inhibited EAC1-3dmo rosettes but failed to inhibit EAC 1-3bmo rosettes. Eight-fold higher concentrations of fluid phase C3d caused partial inhibition of EAC1-3bmo rosette formation with lymphocytes, but not with other types of murine leukocytes. Thus mouse leukocytes apparently contain the same two types of C receptors as do human and guinea pig leukocytes. Mouse CR1 is specific for a non-C3d region of C3b, (possibly analogous to human C3c) whereas mouse CR2 is specific for both C3d and the C3d region of C3b.

Animals↗
PubMed1978

Alternative pathway activation in sickle cell disease and beta-thalassemia major.

Total hemolytic complement activity (CH50), immuno-electrophoretic conversion of Factor B (C3PA), and of C3 were studied in 16 patients with sickle cell disease in a steady state, eight patients in crisis, and ten patients with β-thalassemia major anemia maintained on a constant transfusion regimen. Patients with sickle cell disease in a steady state have moderatley 56 (percent) depressed conversion of Factor B in addition to markedly decreased conversion of C3 in four of ten patients. One of the three sickle cell patients and two of the four thalassemia patients with low C3 conversion levels have died subsequent to the studies. The combination of chronically decreased Factor B conversion in the face of markedly decreased C3 conversion may make these patients occasionally vulnerable to overwhelming infection analagous to the situation seen in postsplenectomy cases.

Adolescent↗
PubMed1978

Immunologic defect of the alternate pathway-of-complement activation postsplenectomy: a possible relation between splenectomy and infection.

Total hemolytic complement (CH50) and activation of the alternate mechanism were measured in eight patients before and after splenectomy and compared to similar measurements made in a control group of patients following other abdominal surgery. In the splenectomy group, alternate-pathway-mediated activation of C3 was significantly different from the controls. The mean five-day postsplenectomy value of 16 percent for the immunoelectrophoretic conversion of C3 to C3i was depressed (p<0.001) from the presplenectomy value of 85 percent and five-month postsplenectomy level of 71 percent (p<0.01). The difference between presplenectomy and five-month postsplenectomy values was not significant. Further, activation of C3 in patients five days postsplenectomy was significantly less (p<0.01) than in the five-day postoperative controls. In both the splenectomized patients and control group, five-day postoperative determinations indicated an increase in CH50 values and a decrease in degree of activation of Factor B. The spleen appears to manufacture certain substances required for activation of C3 via the alternate mechanism. That the manufacture is eventually assumed by other immune-competent organs is shown by the eventual increase of activation toward preoperative levels five months postsplenectomy. This defect in C3 activation may account for the tendency of splenectomized patients to have an increased incidence of bacterial infections and sepsis in the postoperative period.

Adult↗
PubMed1976

Nonspecific complement activation by streptococcal structures. II. Properdin-independent initiation of the alternate pathway.

Complement consumption by isolated membranes and walls from Group A streptococci and various other gram-positive microbes has been tested. These microbial structures were found to activate the alternate complement pathway. However, unlike endotoxin, inulin, or other plant polysaccharides, activation of complement by our material was found to bypass properdin. The activating factor(s) also differs from cobra venom in its/their requirement for factor D. Preliminary experiments suggest this factor isolated from membranes to be a protein and to have a mol wt greater than 40-60,000 daltons. Our studies have led us to speculate that the phylogenetic role of the alternate complement pathway may be the primordial nonspecific defense system which has retained certain fundamental aspects up to the present time.

Antigens, Bacterial↗
PubMed1975

Ultrastructural lesions on the surface of platelets associated with either blood coagulation or with antibody-mediated immune injury.

During blood coagulation ultrastructural lesions were produced on the platelet membrane. They were dependent on the presence of both thrombin and complement (C) and were morphologically identical to the C-dependent ultrastructural lesions (type II) seen in red cells subsequent to activation of C by the alternate mechanismmthough similar in shape they differed in size from ultrastructural lesions (type I) PRODUCED BY ACTIVATION OF C via the classic mechanismmlesions of type I were seen on the platelet surface subsequent to antibody-dependent activation of the C system.

Aluminum Hydroxide↗
PubMed1975

Specificity of human lymphocyte complement receptors.

Erythrocytes, bone marrow-derived lymphocytes, monocytes, and granulocytes were shown to have a receptor activity for C4. Theis C4 receptor activity was studied in relation to the previously identified C3b and C3d receptors. By assay for inhibition of rosette formation by fluid-phase complement (C), only two different lymphocyte C receptors were demonstrated. The immune adherence receptor, the only one of the two shared in common with erythrocytes, was specific for C4 or the C3c region of C3b, but was unreactive with C3d. The other lymphocyte receptor, the C3d receptor, was specific for C3d fragments, but would also react to a lesser extent with the C3d region of uncleaved C3b. ThC3d receptor did not react with either C3c or C4. This specificity of the C3d receptor allowed certain cells which contained only C3d receptors to form rosettes with EAC1-3b and EAC1-3d, but not with EAC14. However, because C3d receptors bound EAC1-3d or C3d fragments more firmly than they did EAC1-3b or C3b fragments, many other types of cells containing only C3d receptors, formed rosettes with EAC1-3d but not with EAC1-3b. Erythrocytes and those lymphocytes which contained only immune adherence receptors, formed rosettes with EAC14 and EAC1-3D but not with EAC1-3d. A double-label assay was devised for the simultaneous detection of both types of C receptors on individual lymphocytes. This assay involved fluorescence labeling of one of the two C receptors with soluble C fragments in combination with the usual rosette method for labeling the other type of C receptor. With this double-label assay, it was observed that the two different lymphocyte C receptors capped independently and thus were located on different molecules which could each move through the fluid membrane matrix independently of the other.

Animals↗