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Biomedical subjects

L H Perrin

Publications and source records attributed to L H Perrin.

At least 55 records · Page 3Linked to original sources
PubMed1984

Independence of complement on in vitro immune phagocytosis of plasmodium falciparum parasitised erythrocytes by human monocytes and polymorphonuclear leukocytes.

Monocytes and polymorphonuclear leukocytes from normal blood donors phagocytosed preferentially Plasmodium falciparum-infected red blood cells (IRBC) in presence of sera from individuals living in areas endemic for malaria. Total complement or factor B heat inactivation of immune or normal serum does not alter opsonic activity directed against IRBC.

Complement System Proteins↗
PubMed1984

Immunization against Plasmodium falciparum asexual blood stages using soluble antigens.

Saimiri sciureus monkeys have been successfully immunized against a human malaria parasite, Plasmodium falciparum, using soluble antigens purified from schizont and merozoite extracts. High levels of antibodies reacting with schizont and merozoite specific polypeptides of 140 and 200 kdaltons were detected in the sera of protected monkeys. The five immunized monkeys survived a challenge infection with 5 X 10(7) parasites inducing a fulminant disease in control monkeys.

Animals↗
PubMed1983

Assessment of immune phagocytosis of Plasmodium falciparum infected red blood cells by human monocytes and polymorphonuclear leukocytes. A method for visualizing infected red blood cells ingested by phagocytes.

A method is described for the visualization of red blood cells infected with Plasmodium falciparum ingested by monocytes or polymorphonuclear leukocytes (PMN) after in vitro incubation. Smears were stained with peroxidase followed by 4,6-diamino-2-phenylindole (DAPI) staining specific for DNA. Monocytes or PMN were identified under normal illumination by the peroxidase stain and the nuclei of these cells as well as the parasites were identified by means of the DAPI stain with ultraviolet light. Using this method we found that monocytes and PMN from normal blood donors preferentially phagocytose plasmodium falciparum infected red blood cells in the presence of sera from subjects living in areas endemic for malaria.

Animals↗
PubMed1983

Partial myeloperoxidase deficiency in preleukemia.

In seven subjects with partial and apparently acquired form of myeloperoxidase (MPO) deficiency, some functional properties of neutrophils (PMNs) were studied. Five patients suffered from preleukemia, one from diabetes mellitus and one from carcinoma of the breast with bone marrow metastases. Intracellular bactericidal activity, oxygen consumption and superoxide radical production were within normal limits. In three patients with preleukemia, the serum opsonic activity was markedly reduced (less than m-3SD) in an autologous system, but normal in the presence of pooled normal serum. Decreased opsonic activity was also found when these patient's sera were assayed in the presence of normal PMNs. Since the levels of IgG and C3 were comparable in the patients' sera and the pooled serum, a deficiency of another unknown opsonin or the presence of an opsonization inhibitor has to be postulated. The partial MPO defect apparently doesn't decrease the intracellular killing of Staphylococcus aureus by PMNs. The known susceptibility to bacterial infections in preleukemia may be explained by the reduction of serum opsonization conducing to a secondary decrease of the ingestion and killing of bacteria by the PMNs.

Blood Bactericidal Activity↗
PubMed1983

Phagocytosis of Plasmodium falciparum-parasitized erythrocytes by human polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMN) from normal blood donors phagocytosed P. falciparum-infected red blood cells (IRBC) to a greater extent than normal RBC under in vitro culture condition. The phagocytic activity of PMN was greatly increased by the addition of sera from individuals living in areas endemic for malaria (immune sera) but not by sera from individuals recovering from a first acute P. falciparum infection. The enhancement of the phagocytic activity was associated with the purified IgG fraction of immune sera and was lost after absorption of IgG on protein A sepharose column of preincubation of the immune sera with IRBC. These experiments suggest that opsonisation of IRBC and their subsequent phagocytosis may be one of the mechanisms involved in the clearance of P. falciparum infection in individuals living in areas endemic for malaria.

Antibodies↗
PubMed1983

Plasmodium falciparum polypeptides released during in vitro cultivation.

Synchronous cultures of Plasmodium falciparum were successively labelled with ((35)S)-methionine and both the supernatants and the pellets of infected red blood cells were collected. The release of TCA-precipitable material in the culture supernatants was low during the development of ring forms and trophozoites, increased during schizogony, and was maximum at the time of schizont rupture and merozoite reinvasion. Analysis of the supernatants by SDS - PAGE and autoradiography showed that both polypeptides common to the various developmental stages of the parasite and schizont/merozoite-specific polypeptides were released. Polypeptides of relative molecular mass 140 000, 82 000 and, to a lower degree, 41 000 were present in high amounts in the culture supernatants. These polypeptides have been shown to be the target of monoclonal antibodies that are able to inhibit the growth of P. falciparum cultures, and may be involved in protective immunity. The released polypeptides may also be used as target antigens in immunodiagnostic tests aiming at the detection of malaria infection.

Antigens↗
PubMed1983

High levels of complement breakdown products in tuberculous pleural effusions.

Pleural fluids from 10 patients with tuberculous pleural effusions contained high levels of small molecular weight breakdown products of C3 (C3d) and of properdin factor B (Ba) when compared to 16 patients with effusions of neoplastic origin (P less than 0.001). The same fluids exhibited overlapping values of haemolytic factor B, classical or alternative pathway-mediated haemolytic activity and native C3. A significant correlation between Ba and lysozyme levels was found in all effusions tested (P less than 0.05). These findings suggest that activation of the complement system is an important aspect of the extensive inflammation and tissue destruction characteristic of human tuberculosis.

Complement Activation↗
PubMed1982

Loculated pleural empyema: identification of complement breakdown products in contiguous sterile pleural fluid.

In view of the recent demonstration of complement consumption in human empyema, we searched for evidence of complement activation in 4 patients presenting initially with sterile postpneumonic effusions, but who were later shown to have contiguous loculated pleural empyemas. These results were compared with those obtained on 13 patients with postpneumonic uncomplicated effusions, and on 13 patients with primary empyema. C3d and Ba, respectively, breakdown products of complement components C3 and Factor B were both significantly elevated in the postpneumonic effusions of the 4 patients with loculated empyemas, when compared with those obtained in postpneumonic uncomplicated effusions (p less than 0.005). Total hemolytic complement activity (CH50) was similar in these 2 groups of pleural effusions. Plasma levels of C3d and Ba were undetectable, and CH50 values were within the same range in all groups of patients. These results suggest that the low molecular weight breakdown products of C3 and Factor B had diffused from the adjacent empyema, where active complement breakdown was occurring, into the sterile postpneumonic effusion. This study provides information about complement catabolism in extravascular sites during infection. The potential usefulness of this approach for the detection of loculated purulent collections is discussed.

Aged↗
PubMed1982

Opsonic activity of human immune serum on in vitro phagocytosis of Plasmodium falciparum infected red blood cells by monocytes.

In vitro human monocytes from normal blood donors ingest red blood cells infected with Plasmodium falciparum more efficiently than normal red blood cells (NRBC). The phagocytic activity of human monocytes for infected red blood cells (IRBC) is greatly enhanced by the addition of immune sera obtained from individuals living in areas with endemic malaria. In contrast, the addition of sera obtained from individuals recovering from a first infection, or pooled normal sera, does not result in increased phagocytosis of IRBC. The phagocytosis enhancing activity of immune sera is associated with the IgG fraction and IgG depleted sera do not stimulate phagocytosis. Enhanced immune serum mediated phagocytosis occurs as a result of opsonization of IRBC. This was demonstrated by experiments in which monocytes or IRBC were preincubated with immune serum prior to the phagocytic assay. The opsonic activity could be absorbed by IRBC but not by NRBC. The opsonization of IRBC and subsequent phagocytosis were also dependent on the stage of development of the intracellular parasite. IRBC containing schizonts and trophozoites were preferentially phagocytosed as compared with ring forms. The role of malaria induced surface alterations and/or malaria surface antigens in the opsonization of IRBC by immune sera is discussed. These experiments suggest that phagocytosis of P. falciparum IRBC by monocytes may play a role in the immune elimination of malaria infection in humans.

Erythrocytes↗
PubMed1981

Inhibition of P. falciparum growth in human erythrocytes by monoclonal antibodies.

Malaria is increasing in incidence and prevalence in most tropical areas and is a major problem for both individuals and communities. Current malaria research is aimed at developing vaccines and, for this, it may be useful to define Plasmodium antigen(s) related to the development of a protective immune response in the host. Monoclonal antibodies have recently been shown to interfere with rodent malaria infection (Plasmodium berghei) at the sporozoite or merozoite stage. We have now raised monoclonal antibodies against single antigenic determinant(s) of Plasmodium falciparum and report that some of them inhibit the growth of erythrocytic forms of P. falciparum in vitro.

Animals↗
PubMed1981

Decreased capacity to solubilize immune complexes in sera from patients with systemic lupus erythematosus.

The capacity to solubilize immune complexes formed in vitro is significantly decreased in patients with systemic lupus erythematosus (SLE). This complement function correlates significantly with serum C3 levels and inversely with the presence of circulating immune complexes. Clinically, patients with a decreased capacity, to solubilize complexes show a worse evolution and an increased incidence of renal involvement. In conclusion, the impaired solubilization capacity, related to low complement activity, which is observed in patients with SLE may favor the persistence of immune complexes in tissues.

Antigen-Antibody Complex↗
PubMed1980

Evaluation of alternative pathway and factor B haemolytic activities in patients with systemic lupus erythematosus: correlations with the alternative pathway regulatory proteins.

The haemolytic activities of the complement alternative pathway and factor B were studied using a 51Cr-release assay in 77 sera from patients with systemic lupus erythematosus (SLE). These values were compared to those of several complement components and of the regulatory proteins beta H and C3b INA. There was a significant decrease in the alternative pathway activity, which correlated with a decrease in the haemolytic activity of factor B and with the activity of the classical pathway. There was a significant decrease in the level of one regulatory protein beta 1H, while the level of the other regulatory protein, C3b INA, was increased; however, there was a positive correlation between these two parameters. The results obtained suggest that the decreased activity of the alternative pathway observed in SLE reflects a consumption due to a triggering of the C3b amplification loop through the activation of the classical pathway. In one patient, an acquired deficiency of the capacity to activate the alternative pathway in the presence of inulin was observed.

Adult↗
PubMed1980

Demonstration of a local exhaustion of complement components and of an enzymatic degradation of immunoglobulins in pleural empyema: a possible factor favouring the persistence of local bacterial infections.

Local bacterial infections such as abscesses or purulent exudates most often contain numerous, easily culturable bacteria despite an intense inflammatory reaction characterized by the ingress of polymorphonuclear leucocytes. In order to understand the mechanisms leading to such a persistent infection, we used pleural empyema as a model and measured the levels and catabolism of complement as well as of immunoglobulins in 28 infectious pleural effusions associated with either a positive or with a negative bacterial culture. Classic and alternative pathway haemolytic activities, factor B and C4 haemolytic activities as well as native C3 were markedly decreased or undetectable in most culture-positive effusions when compared to culture-negative effusions (P less than 0.005); breakdown products of factor B and C3 were markedly increased in culture-positive fluids. Eleven out of 14 culture-positive fluids exhibited IgG breakdown as opposed to none of the culture-negative fluids. In seven out of 14 culture-positive fluids, incubation with 125I-IgG led to their in vitro breakdown. This proteolytic activity could be abolished by preincubation of the culture-positive fluids with normal sera. Thus, increased catabolism of complement and breakdown of immunoglobulins, both leading to local consumption of immune reactants, could be one of the causes for bacterial persistence in pleural empyema.

Complement C3↗