No description available.

No description available.

A properdina tem a capacidade de estabilizar o complexo enzimático C3bBb, com função de C3-convertase da Via Alternativa, capaz de clivar moléculas de C3, gerando C3a e C3b. Diferentes trabalhos têm sugerido que a properdina pode se ligar diretamente à superficie de um patógeno independentemente complexo enzimático C3bBb. No que diz respeito à interação de properdina com Leptospira tanto patogênica quanto não patogênica, nada se conhece na literatura. Neste trabalho demostramos que tanto a properdina presente no SHN, quanto purificada e todos os seus oligômeros interagiram com tais espiroquetas. Também observamos que a ligação da properdina pode acontecer diretamente na superfície da bactéria ou após ligação prévia do fragmento C3b. Observamos também, que na presença de SHN estas bactérias foram totalmente eliminadas, no entanto, 70% das bactérias sobreviveram quando incubadas com SHD-P. Já a adição de properdina purificada ao SHD-P provoca uma marcante diminuição no número de leptospiras viáveis. Avaliamos também quais proteínas bacterianas teriam a capacidade de se ligar à properdina. Entre as proteínas recombinantes de L. interrogans, apenas a lipoproteína LIC11087, uma proteína presente unicamente na superfície de leptospiras patogênicas, interagiu com a properdina. Todos os oligômeros de properdina presentes no SHN interagiram com a lipoproteína LIC11087. Determinamos por quantificação do complexo enzimático usando anti-Factor B policlonal que a properdina apresenta uma significativa atividade reguladora quando se depositava na superfície das bactérias não patogênicas, promovendo desta maneira, a formação da C3-convertase da Via Alternativa. Constatamos também nos sorovares patogênicos, pouca atividade reguladora pela properdina quando estas leptospiras foram pré-incubadas com a proteína. Também encontramos que a ligação da properdina na superfície de leptospiras contribui para um aumento da fagocitose por polimorfonucleares humanos de leptospiras, principalmente das não patogênicas. Nossos dados obtidos até o momento sugerem que a properdina liga-se na superfície das leptospiras patogênicas e não patogênicas; participa no processo de eliminação de leptospiras não patogênicas pela Via Alternativa; e, após sua deposição na superfície das bactérias, contribui para a formação de uma C3-convertase nas bactérias não patogênicas, diferente ao modelo tradicional. / Properdin is a positive regulatory protein that stabilizes the C3- and C5-convertases of the alternative pathway. Several studies have suggested that properdin can bind directly to the surface of a pathogen regardless enzyme complex C3bBb. With regard to the interaction of properdin with both pathogenic Leptospira and non-pathogenic, nothing is known in the literature. In this work we demonstrate that both properdin present in SHN and purified and all their oligomers interacted with spirochetes and of properdin can binding directly on the surface of bacteria or after prior binding of C3b fragment. We also observed that the Activation of the alternative pathway of complement is crucial for killing non-pathogenic L. biflexa and properdin acts effectively since this bacterium proliferates in P-depleted human serum. Since the addition of purified properdin the SHD-P causes a marked decrease in the number of viable leptospires. We also evaluated bacterial proteins which have the ability to bind to properdin. Among several recombinant leptospiral membrane proteins tested, lipoprotein LIC11087, present only in pathogenic Leptospira, was the ligand for P, P2, P3 and P4. Determined by quantifying the enzyme complex using polyclonal anti-factor B that properdin presents a significant regulatory activity when deposited on the surface of non-pathogenic bacteria, thereby promoting the formation of C3 convertase Alternative pathway. We found also in pathogenic serovars, little regulatory activity by properdin when they were preincubated leptospires with the protein. We also found that the binding of properdin in leptospiras surface contributes to increased phagocytosis of leptospira by human polymorphonuclear, mainly from non-pathogenic. Our data obtained suggest that properdin binds to Leptospira species and may play an important role to limit the proliferation of non-pathogenic Leptospira; participates in leptospiras elimination process nonpathogenic Via Alternative; and, after deposition on the surface of bacteria, it contributes to the formation of a C3 convertase in non-pathogenic bacteria, different from the traditional model.

Neutrophils play an important, yet poorly understood role, in complement mediated pathologies. Here we identified that neutrophils contain key components from the complement alternative pathway: properdin (CFP), complement component 3 (C3), complement factor B (CFB), and complement factor H (CFH). Activation of neutrophils resulted in secretion of these complement components. When neutrophils are further activated to form neutrophil extracellular traps (NETs), CFP is deposited onto the surfaces of the NETs. In addition, CFP is able to bind to Pseudomonas aeruginosa, an opportunistic bacterium which can activate neutrophils to form NETs. Furthermore, NETs activate complement and increase formation of the terminal complement complex. The activation of complement on NETs can be initiated through multiple pathways, however, activation of the alternative pathway is dependent on CFP. This mechanism, potentially required for effective host defense, may also contribute to complement activation and disease.

Neutrophils play an important, yet poorly understood role, in complement mediated pathologies. Here we identified that neutrophils contain key components from the complement alternative pathway: properdin (CFP), complement component 3 (C3), complement factor B (CFB), and complement factor H (CFH). Activation of neutrophils resulted in secretion of these complement components. When neutrophils are further activated to form neutrophil extracellular traps (NETs), CFP is deposited onto the surfaces of the NETs. In addition, CFP is able to bind to Pseudomonas aeruginosa, an opportunistic bacterium which can activate neutrophils to form NETs. Furthermore, NETs activate complement and increase formation of the terminal complement complex. The activation of complement on NETs can be initiated through multiple pathways, however, activation of the alternative pathway is dependent on CFP. This mechanism, potentially required for effective host defense, may also contribute to complement activation and disease.

A properdina tem a capacidade de estabilizar o complexo enzimático C3bBb, com função de C3-convertase da Via Alternativa, capaz de clivar moléculas de C3, gerando C3a e C3b. Diferentes trabalhos têm sugerido que a properdina pode se ligar diretamente à superficie de um patógeno independentemente complexo enzimático C3bBb. No que diz respeito à interação de properdina com Leptospira tanto patogênica quanto não patogênica, nada se conhece na literatura. Neste trabalho demostramos que tanto a properdina presente no SHN, quanto purificada e todos os seus oligômeros interagiram com tais espiroquetas. Também observamos que a ligação da properdina pode acontecer diretamente na superfície da bactéria ou após ligação prévia do fragmento C3b. Observamos também, que na presença de SHN estas bactérias foram totalmente eliminadas, no entanto, 70% das bactérias sobreviveram quando incubadas com SHD-P. Já a adição de properdina purificada ao SHD-P provoca uma marcante diminuição no número de leptospiras viáveis. Avaliamos também quais proteínas bacterianas teriam a capacidade de se ligar à properdina. Entre as proteínas recombinantes de L. interrogans, apenas a lipoproteína LIC11087, uma proteína presente unicamente na superfície de leptospiras patogênicas, interagiu com a properdina. Todos os oligômeros de properdina presentes no SHN interagiram com a lipoproteína LIC11087. Determinamos por quantificação do complexo enzimático usando anti-Factor B policlonal que a properdina apresenta uma significativa atividade reguladora quando se depositava na superfície das bactérias não patogênicas, promovendo desta maneira, a formação da C3-convertase da Via Alternativa. Constatamos também nos sorovares patogênicos, pouca atividade reguladora pela properdina quando estas leptospiras foram pré-incubadas com a proteína. Também encontramos que a ligação da properdina na superfície de leptospiras contribui para um aumento da fagocitose por polimorfonucleares humanos de leptospiras, principalmente das não patogênicas. Nossos dados obtidos até o momento sugerem que a properdina liga-se na superfície das leptospiras patogênicas e não patogênicas; participa no processo de eliminação de leptospiras não patogênicas pela Via Alternativa; e, após sua deposição na superfície das bactérias, contribui para a formação de uma C3-convertase nas bactérias não patogênicas, diferente ao modelo tradicional. / Properdin is a positive regulatory protein that stabilizes the C3- and C5-convertases of the alternative pathway. Several studies have suggested that properdin can bind directly to the surface of a pathogen regardless enzyme complex C3bBb. With regard to the interaction of properdin with both pathogenic Leptospira and non-pathogenic, nothing is known in the literature. In this work we demonstrate that both properdin present in SHN and purified and all their oligomers interacted with spirochetes and of properdin can binding directly on the surface of bacteria or after prior binding of C3b fragment. We also observed that the Activation of the alternative pathway of complement is crucial for killing non-pathogenic L. biflexa and properdin acts effectively since this bacterium proliferates in P-depleted human serum. Since the addition of purified properdin the SHD-P causes a marked decrease in the number of viable leptospires. We also evaluated bacterial proteins which have the ability to bind to properdin. Among several recombinant leptospiral membrane proteins tested, lipoprotein LIC11087, present only in pathogenic Leptospira, was the ligand for P, P2, P3 and P4. Determined by quantifying the enzyme complex using polyclonal anti-factor B that properdin presents a significant regulatory activity when deposited on the surface of non-pathogenic bacteria, thereby promoting the formation of C3 convertase Alternative pathway. We found also in pathogenic serovars, little regulatory activity by properdin when they were preincubated leptospires with the protein. We also found that the binding of properdin in leptospiras surface contributes to increased phagocytosis of leptospira by human polymorphonuclear, mainly from non-pathogenic. Our data obtained suggest that properdin binds to Leptospira species and may play an important role to limit the proliferation of non-pathogenic Leptospira; participates in leptospiras elimination process nonpathogenic Via Alternative; and, after deposition on the surface of bacteria, it contributes to the formation of a C3 convertase in non-pathogenic bacteria, different from the traditional model.

No description available.

No description available.

No description available.

Genetic as well as environmental factors are believed to be of importance in the etiology of rheumatoid arthritis (RA). There are a number of previous studies of genetic markers in RA, but so far no genetic linkage and only a few associations have been found. Of the associations only one (with the HLA antigen DR4) appears to be well documented. In most previous association studies the patients have not been divided according to sex and family history of RA. In this investigation the HLA antigens A, B and DR and five serum protein systems (Bf, C3, Pi, Hp and Tf) were studied in patients with erosive rheumatoid arthritis (RA), from northern Sweden. Special attention was paid to variations in the strength of associations accord­ing to sex and family history of polyarthritis. The following results were found:  The frequency of the HLA antigen B27 was significantly increased in the North-Swedish population (16.6%) and among patients with a family history of polyarthritis (42.6%). In agree­ment with previous investigations a significantly increased frequency of the DR4 antigen was found in the RA patients.  In the properdin factor B (Bf) system the S phenotype was found to be significantly in­creased in male patients and in patients with a family history of polyarthritis, more severe form of RA and high titres of rheumatoid factor.  No significant differences with respect to phenotype or gene frequencies were found in the C3 complement system. Thus, the association between RA and C3 found in previous investiga­tions was not confirmed.  A significant increase of rare alpha-1-antitrypsin (Pi) types (MS, MZ, MF and SZ) was found among RA patients. However, the increase concerned mainly Z heterozygotes and was more strongly pronounced among male patients.  In the haptoglobin system a significant increase of the Hp^ gene and the Hp2-2 type was found among patients with a family history of polyarthritis, more pronounced among males.  A significant increase of the transferrin gene and of the 2 type was found among male RA patients, more pronounced among patients with a family history of polyarthritis. In 6 out of 8 gene loci studied significant associations were found, which is in agreement with a multifactorial etiology of RA. The results were largely in agreement with the hypothesis that associations would be expected to be stronger in males and in patients with a family history of polyarthritis. A notable finding was the high frequency of first degree relatives (around 40%) with symmetric peripheral polyarthritis of which more than 70% had a diagnosis of RA verified by hospital records. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1985, härtill 6 uppsatser.</p> / digitalisering@umu