Novel perspectives on the pathogenesis of Lonomia obliqua caterpillar envenomation based on assessment of host response by gene expression analysis.
Animal venomous secretions have been explored as source of active substances affecting mammal hemostasis. These active principles impinge on key elements of almost all physiologic pathways and have an enormous potential in the development of new therapeutic drugs. The envenomation caused by the caterpillar Lonomia obliqua (lonomism) is characterized by a hemorrhagic clinical profile. Investigations of caterpillar venom have, in general, involved the isolation and biochemical characterization of active principles related to the pathophysiology of envenomation. In the last few years, these studies focused on the caterpillar's secretions pro-coagulant, fibrin(ogen)olytic, hemolytic, edematogenic and nociceptive activities. Recently, a significant advance was achieved as a result of a transcriptome study, which generated a catalog of putative toxic proteins in the caterpillar venom, giving rise to hypotheses on the molecular basis of pathogenesis which could be experimentally explored. In this investigation, using a microarray methodology, we analyzed the effects of the caterpillar venom on the gene expression profile of cultured human fibroblasts with the aim of gaining insight into genes possibly associated with the clinical manifestations of lonomism. Our hypothesis was that both the direct action L. obliqua venomous proteins on the host as well as an indirect effect caused by alteration in the gene expression pattern in host tissues could function in concert and perhaps synergistically to give rise to the profound symptoms observed during lonomism. Interesting changes in the expression pattern of some genes, such as IL-8, prostaglandin-endoperoxide synthase 2, urokinase-type plasminogen activator receptor and tissue factor, were observed in treated fibroblasts, which could contribute to some of the observed pathological sequela in lonomism. Thus, lonomism appears to be a result of both the previously described direct effects of the venom as well as indirect effects caused by changes in host gene expression profiles. These studies have enhanced our understanding of lonomism and may contribute to insights into more effective treatments.
Pinto
Antônio F M
AF
Department of Microbiology, University of Virginia, P.O. Box 800734, Charlottesville, VA 22908-0734, USA.
Dragulev
Bojan
B
Guimarães
Jorge A
JA
Fox
Jay W
JW
D000818:Animals; D001180:Arthropod Venoms / Q000633:toxicity*; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007915:Lepidoptera / Q000472:pathogenicity / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment
D001180:Arthropod Venoms; D016209:Interleukin-8; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human