Paf-Metabolic Enzymes and Paf-like Activity inL. InfantumandL. MajorPromastigotes

Abstract

Leishmania spp are obligate intracellular protozoan parasites of the mononuclear phagocyte system that cause a spectrum of diseases known as leishmaniasis. Platelet Activating Factor (PAF) and some PAF-antagonists seem to play a key role in Leishmania infection. In this article we detected for the first time the specific activities of PAF basic metabolic enzymes, PAF cholinephosphotransferase (PAF-CPT) and Lyso-PAF-acetylotransferase (Lyso-PAF-AT), in two species of Leishmania, namely Leishmania major (L. major) and Leishmania infantum (L. infantum). Specific activity of PAF-CPT of L. major homogenates was substantially higher than that of L. infantum homogenates, while Lyso-PAF-AT specific activities of the homogenates of both species were detected in the same levels. In addition, PAF-like molecules were detected in cells and their culture medium of both species. These results show that PAF-biosynthesis exists and varies between Leishmania species, findings that are in correlation with the general idea that the presence of PAF in several Leishmania species is implicated in Leishmania infection.

Inflammation, not Cholesterol, Is a Cause of Chronic Disease

“…Many diseases develop as an adverse consequence of an imbalanced inflammatory response; thus, chronic and unresolved infections are usually accompanied by chronic and unresolved inflammatory manifestations and comorbidities [ 206 ]. PAF and PAF-like molecules are implicated in inflammatory manifestations occurring in several infections [ 206 , 207 ], such as HIV [ 69 , 70 , 71 , 72 , 73 , 74 , 85 ], leishmaniosis [ 208 ], periodontitis [ 75 , 76 , 77 ], or even in sepsis [ 67 , 209 ]. The relationship between increased PAF levels, overexpression of PAF-R, and the PAF/PAF-R pathways with several other mediators such as cytokines and inflammatory cells leads to the progression of such diseases and their related comorbidities.…”

“…The most common coexistent diseases associated with chronic infections are CVD, CNS disorders, and tumour malignancies, which are usually promoted by increased levels of PAF and PAF-related continuous and unresolved inflammation [ 57 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 85 , 208 ]. In addition, PAF seems to act in synergy with infectious agents to initiate and propagate the disease process, i.e., viral load in HIV-infected patients was positively correlated with PAF synthesis and levels, while viral products such as Tat-protein induce PAF synthesis and PAF-related HIV-induced non-AIDS comorbidities, such as CVD, Kaposi sarcoma, neurodegeneration, and dementia [ 69 , 70 , 71 , 72 , 73 , 74 ].…”

IL-36 Receptor Antagonist with Special Emphasis on IL-38

“…In these inflammatory and other autoimmune diseases the number ofcirculating lymphocytes T-helper 17 (ThI7) is increased with high production of IL-17A, IL-21, and IL-22 (85)(86)(87)(88). In fact, IL-38 plays a role in MAPK activation which is further enhanced by the stimulation through toll-like receptor, resulting in the enhanced proinflammatory cytokine production (89)(90)(91)(92).…”

Tin(II) and Tin(IV) Complexes Incorporating the Oxygen Tripodal Ligands [(η5-C5R5)Co{P(OEt)2O}3]−, (R = H, Me; Et = -C2H5) as Potent Inflammatory Mediator Inhibitors: Cytotoxic Properties and Biological Activities against the Platelet-Activating Factor (PAF) and Thrombin

“…The PAF-like pathway-related aggregatory effects of samples on rabbit platelets are expressed as the concentrations of PAF that can induce the same effect of 50% of platelet aggregation, also known as the concentration effective in producing 50% of the maximal response (EC 50 values) [ 63 , 64 , 65 ]. Biological assays were performed several times ( n > 6) to ensure the validity of results.…”