As the gene moves between special regions in the nucleus, the frequency of switching changes. Skip to content News. News Menu. Beyond leukocytes and lymphocytes, endothelial cells also play a crucial role in the inflammatory response during severe malaria. In the erythrocytic phase, endothelial activation accounts for many factors involved in the development of severe malaria [ 49 ], such as increased adhesion of infected RBCs [ 50 ], increased expression of chemokines [ 51 ], and increased adhesion of leukocytes to peripheral organ microvasculature [ 52 ].
Several soluble proteins have been described such as inflammatory markers of endothelial activation during severe malaria. The angiopoietin Ang -Tie2 axis is a critical regulator of endothelial quiescence, activation and dysfunction in infectious and oncologic diseases, atherosclerosis, and pulmonary hypertension [ 53 , 54 ]. Ang-1 signals through its cognate receptor Tie-2 a tyrosine kinase with immunoglobulin and endothelial growth factor homology domains , which is expressed on endothelial cells [ 53 ].
During cerebral malaria CM , Ang-1 exerts anti-inflammatory effects by decreasing adhesion molecule expression and maintaining the integrity of the BBB by reinforcing VE-cadherin tight junctions [ 53 , 54 ]. In contrast, Ang-2 is stored in Weibel-Palade bodies WPB within endothelial cells and is involved in the response to inflammatory stimuli.
High levels of Ang-2 are observed in children with severe malaria [ 56 ]. In healthy subjects, the basal Ang-1 level is higher than that of Ang-2, while the opposite ratio is observed in fatal cases of severe malaria [ 57 ]. Another inflammatory marker of endothelial activation during sever malaria is the activation of endothelial cell protein C receptor EPCR. EPCR is widely expressed on endothelial cells and leukocytes, and its activation is associated with severe malaria [ 58 , 59 ].
EPCR is referred to as the cell surface conductor of cytoprotective coagulation factor signaling because it enhances the conversion of protein C into its activated state, activated protein C APC.
The inflammatory features described above occur in different organs and at different intensities. Although there are few examples of leukocyte adhesion in the brain vasculature in the development of human cerebral malaria [ 62 ], necropsy in fatal cases of severe malaria reveals marked inflammatory cell infiltration in lung tissue [ 11 ].
However, the malaria-induced inflammatory response that is responsible for kidney dysfunction is not related to inflammatory cell accumulation in renal tissue but depends on immunocomplex deposition and infected RBC adhesion to the renal vasculature [ 63 ]. Cerebral malaria is mainly attributed to P.
Cerebral complications during malaria are triggered by the mechanisms described above; however, the inflammatory response observed in the brain is unique.
Taylor and coworkers have been studying the pathogenesis of cerebral malaria CM and have observed three different pathologies: i CM1—presence of sequestered parasitized erythrocytes in the cerebral microvasculature; ii CM2—presence of sequestered parasitized erythrocytes in the cerebral microvasculature and vascular pathology; and iii CM3—non-malarial components involved in cerebral damage.
Inflammatory mediators are involved in CM1 and CM2. As described above, adhesion molecules and EPCR expressed in brain endothelial cells induce parasitized erythrocyte adhesion [ 58 ]. Likewise, during CM2, leukocytes are observed in the intravascular space, and plasmatic proteins are found in the brain tissue, suggesting edema formation [ 62 ]. The role of leukocytes in the pathogenesis of cerebral malaria is unclear.
A main characteristic of brain anatomy is the presence of the BBB, which confers protection against circulating cell diapedesis into brain tissue. Nevertheless, the BBB composition of postcapillary venules allows leukocyte diapedesis during non-malarial brain injury [ 65 , 66 ]. However, leukocytes are not observed within brain tissue during CM2 [ 62 , 67 ], suggesting an indirect contribution of these cells to the development of cerebral malaria. Cytokine production by leukocytes during P.
Inflammatory response during cerebral malaria—during cerebral malaria, it is possible to observe the presence of sequestered parasitized erythrocytes in the cerebral microvasculature, vascular pathology, leukocytes in the intravascular space and plasmatic proteins in brain tissue, suggesting edema formation.
Figure created in the Mind the Graph platform www. Although experimental models of severe malaria could not be used to predict human pathology, they have been extensively used to elucidate cellular and molecular pathophysiological processes. Several findings observed in human cerebral malaria are also observed in experimental models, including cytokine activity [ 70 ], endothelial activation [ 71 ], and edema formation [ 72 ]; however, the sequestration of parasitized erythrocytes during experimental cerebral malaria ECM is not well understood.
In addition, another study suggests transient contact between infected RBCs and the endothelium [ 74 ]. The expression of Pf-erythrocyte membrane protein EMP s and their ability to adhere to host adhesion molecules depends on the expression of structural proteins, such as knob-associated histidine-rich protein KAHRP , that allow the formation of knobs on erythrocyte membranes [ 75 ].
Plasmodium species incapable of forming knobs in infected erythrocytes knobless Plasmodium show a passive adhesion of infected RBCs to activated endothelial cells [ 75 ]. Thus, knobless Plasmodium activates endothelial cells to the same extent as knob-forming Plasmodium [ 66 , 73 ], which suggests that ECM may also be induced by parasitized erythrocytes. Amyloid-beta accumulation caused by chloroquine injections precedes ER stress and auto phagosome formation in rat skeletal muscle.
Acta Neuropathol. Regillo CD. Basic and clinical science course, section retina and vitreous Chloroquine cardiomyopathy a review of the literature. Immunopharmacol Immunotoxicol. Chloroquine neuromyopathy.
One case in prophylactic malariatherapy. Nouv Presse Med. A simple method for assessing quinine pre-treatment in acute malaria. Quinine-induced arrhythmia in a patient with severe malaria. Acta Med Indonesia. Fatal quinine cardiotoxicity in the treatment of falciparum malaria. The antimalarial drug artesunate inhibits primary human cultured airway smooth muscle cell proliferation.
Functional significance of increased airway smooth muscle in asthma and COPD. J Appl Physiol. Skeletal muscle troponin as a novel biomarker to enhance assessment of the impact of strength training on fall prevention in the older adults. Nurs Res. Download references. MTM conceived and wrote the first draft of the article. MAB helped with its design and content and with coordination of the draft manuscript.
Both authors read and approved the final manuscript. Jay Endowment MB. You can also search for this author in PubMed Google Scholar. Correspondence to Mauro Toledo Marrelli. Reprints and Permissions. Marrelli, M. The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles. Malar J 15, Download citation. Received : 30 March Accepted : 28 October Published : 02 November Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Abstract Malaria remains one of the most important infectious diseases in the world, being a significant public health problem associated with poverty and it is one of the main obstacles to the economy of an endemic country.
Background Malaria remains as the most important human infectious diseases in the World, with around million cases a year, and an astounding , deaths resulting from this disease alone [ 1 ]. Malaria affecting skeletal muscles The detrimental effects of the causing malaria agents on skeletal muscles in animals and humans are well known [ 11 , 16 — 20 ].
Full size image. Effects of malaria on cardiac muscle Few studies have been focused on cardiac effect in severe malaria [ 25 — 27 ] despite serious symptoms of coronary complications have been observed in severe malaria patients. Anti-malarial drugs and their effects on cardiac and skeletal muscles Treatment for malaria disease can only be initiated after making the correct diagnosis. Conclusion Long-term impacts of malaria include death, disability, and significant socioeconomic burden on societies where the disease is prevalent.
References 1. Article PubMed Google Scholar 4. Article PubMed Google Scholar 8. Google Scholar Article PubMed Google Scholar PubMed Google Scholar CAS Google Scholar Article Google Scholar Acknowledgements We are thankful to Ms. Heather Maxwell for proof reading the manuscript. Competing interests Both authors declare that they have no competing interests. View author publications. About this article. Cite this article Marrelli, M. Bennett JE, et al.
Malaria plasmodium species. Elsevier; Accessed Dec. Merck Manual Professional Version. Brunette GW, et al. Oxford University Press; Breman JG.
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