Inactivation of C5a Anaphylatoxin by a Peptide That Is Complementary to a Region of C5a

Fujita, Emiko; Farkas, Imre; Campbell, William; Baranyi, Lajos; Okada, Hidechika; Okada, Noriko

doi:10.4049/jimmunol.172.10.6382

Cited by 38 publications

(26 citation statements)

References 19 publications

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“…Therefore, we generated complementary peptides to PL37 with the software program MIMETIC (4), based on its previous success at generating complementary peptides inhibitory to HIV-1 reverse transcriptase (4,12) and thrombomodulin (20). PepA, one of the complementary peptides targeting PL37, has shown an appreciable capacity to interfere with C5a function (10). The sequence of PL37 was that of human C5a, and the amino acid sequence homology to the corresponding portion of rat C5a was 56%.…”

Section: Discussionmentioning

confidence: 99%

Increased Inhibitory Capacity of an Anti‐C5a Complementary Peptide Following Acetylation of N‐terminal Alanine

Okada

Asai

Hotta

et al. 2007

Microbiology and Immunology

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Amino acids 37 to 53 (RAARISLGPRCIKAFTE) of C5a anaphylatoxin form an essential region for C5a function. To target this sequence, we generated a complementary peptide (ASGAPAPGPAGPLRPMF) designated PepA which has a potent inhibitory effect on C5a activity. By introducing an acetyl group at the N‐terminal alanine of PepA, an acetylated form was generated which was designated AcPepA. The acetylation resulted in increased inhibition of C5a stimulation of neutrophils as determined by Ca influx. Furthermore, AcPepA partially inhibited the lethal shock induced in mice by intravenous administration of Candida albicans water‐soluble mannoprotein‐β‐glucan complex. In addition, local skin inflammation in rats caused by an anti‐Crry monoclonal antibody was suppressed when AcPepA and the antibody were injected together, while PepA had little inhibitory capacity. The potent inhibitory capacity of AcPepA was also confirmed by a skin reaction of guinea pigs inoculated with recombinant human C5a together with AcPepA.

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Section: Discussionmentioning

confidence: 99%

Increased Inhibitory Capacity of an Anti‐C5a Complementary Peptide Following Acetylation of N‐terminal Alanine

Okada

Asai

Hotta

et al. 2007

Microbiology and Immunology

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“…Since the co-addition of C3a did not significantly potentiate cysLT generation when compared with IgE and anti-IgE antibody alone, it remains to be determined whether acetylated peptide A precisely antagonized C3a activity. This peptide has been shown to inhibit the action of C5a in human neutrophils, in a human cell line, and in an in vivo C5a-induced rat shock model (10). Since this novel C5a inhibitor appears to inhibit the C5a reaction in human lung tissues, it may be useful for suppressing allergic inflammation in human lungs.…”

Section: Resultsmentioning

confidence: 99%

“…Human purified IgE and goat anti-human IgE antibody were purchased from Chemicon International (Temecula, Calif., U.S.A.). A complementary peptide of C5a named as Pep A (ASGA-PAPGPAGPLRPMF) is a complementary peptide to amino acids 33 to 53 of human C5a (6,10,12). Its Nterminal alanine was acetylated and named as acetylated Pep A, as reported elsewhere (Asai et al, in submission).…”

Section: Methodsmentioning

confidence: 99%

Contribution of Anaphylatoxins to Allergic Inflammation in Human Lungs

Abe

Hama

Shirakusa

et al. 2005

Microbiology and Immunology

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The contribution of complement activation to allergic asthma remains controversial. In order to elucidate the role played by the complement split products, anaphylatoxins C3a and C5a, we evaluated their effects on production of cysteinyl‐leukotrienes (cysLTs) by human lung fragments following an anaphylactic reaction. The lung tissues obtained from two patients with lung cancer showed C5aR‐, C5L2R‐, and C3aR‐mRNA expression. When the chopped lung fragments passively sensitized with human IgE were incubated with anti‐human IgE antibody, a significant amount of cysLTs was generated in comparison with the control (without anti‐IgE antibody). The co‐addition of human C5a at doses of 0.1 to 10 ng/ml to the anti‐IgE antibody potentiated cysLT production. The response was bell‐shaped in distribution, significant, and peaked at a C5a concentration of 1 ng/ml. The co‐addition of human C3a up to 1,000 ng/ml seemed to increase cysLT production, but not to any significant extent. A novel C5a receptor complementary peptide, acetylated peptide A, dose‐dependently inhibited cysLT production by the human lung fragments following the anaphylactic reaction in the presence of 1 ng/ml C5a. However, this peptide did not inhibit cysLT production in the presence of 100 ng/ml C3a. It is suggested that the anaphylatoxin C5a potentiates cysLT production in human lung tissues and contributes to allergic inflammation in disorders such as asthma, thus acetylated peptide A may be useful for suppressing allergic inflammation in the lungs.

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“…Previous demonstration showed that the classical complement pathway was also activated on the surface of human islets that reacted with ABO-compatible blood involving IgG, IgM and other complement proteins, namely C3, C4 and C9, thus emphasizing the significance of immunoglobulins in the activation of complement cascade 23 . In contrast to other complement proteins, C5a has been proposed as a critical molecule responsible for the initiation of coagulation and inflammation by intervening TF expression in neutrophils 24,25 . Compstatin -a complement inhibitor treatment significantly improved the graft survival under in vivo conditions 26 .…”

Section: Hurdles Faced During Pancreatic Islet Transplantationmentioning

confidence: 99%

Clinical Islet Cell Transplantation – Recent Advances

Saravanan¹,

Loganathan²,

Naziruddin³

et al. 2017

Current Science

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Type-1 diabetes mellitus (T1DM) caused by autoimmune destruction of insulin-producing beta-cells essentially requires treatment with exogenous insulin therapy. Despite the education, technology and improvements in insulin formulations, patients face the ongoing life-threatening hypoglycaemia with poor quality of life as well as progressive disease leading to microand macro-vascular complications of diabetes. Islet transplantation offers an alternative therapeutic option for these patients. In this review, we discuss the recent advancements in this field tracking from the history of pancreatic islet transplantation to the present-day challenges of clinical islet cell transplantation. We summarize the cutting-edge clinical research with special reference to the results of current trials, including Clinical Islet Transplant Consortium, improvements in immunosuppressive protocols, the need for beta-cell replacement therapies, including the application of induced pluripotent stem cells and mesenchymal stem cells.

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Inactivation of C5a Anaphylatoxin by a Peptide That Is Complementary to a Region of C5a

Cited by 38 publications

References 19 publications

Increased Inhibitory Capacity of an Anti‐C5a Complementary Peptide Following Acetylation of N‐terminal Alanine

Increased Inhibitory Capacity of an Anti‐C5a Complementary Peptide Following Acetylation of N‐terminal Alanine

Contribution of Anaphylatoxins to Allergic Inflammation in Human Lungs

Clinical Islet Cell Transplantation – Recent Advances

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