Pulmonary Inflammation and Edema Induced by Phospholipase A2

Abstract

Victims of snakebite quickly succumb to severe respiratory failure, which can be fatal if left untreated. One of the most toxic components of snake venom is phospholipase A 2 (PLA 2 ; EC 3.1.1.4). PLA 2 isolated from the elapid, Naja sputatrix, induced pulmonary inflammation and edema when administered intravenously and intratracheally to rats. Analysis of pulmonary gene expression profiles using oligonucleotide microarrays revealed 60 genes whose expression was altered by at least 3-fold in response to intratracheal instillation of PLA 2 for 3 h as compared with controls. In addition to genes encoding cytokines and chemokines responsible for inflammatory processes, the Na ؉ /K ؉ -ATPase gene has been found to be involved in edema formation. Real-time PCR, Western blot, and immunohistochemical analyses confirmed that the expression of AQP1 and AQP5 mRNAs and proteins was decreased. Besides providing an experimental model for studies on the pathophysiology of the lung, this investigation yields a clue to the mechanisms by which endogenous PLA 2 s could mediate inflammation in conditions such as allergy and rheumatoid arthritis.

Naja annulifera Snake: New insights into the venom components and pathogenesis of envenomation

“…The inflammatory events promoted by the venom may be attributed to hyaluronidase, PLA 2 , glycosylated proteins, SVSP and SVMP since they can promote different inflammatory events, which include complement activation, mast cell degranulation, release of eicosanoids and cytokines and leukocyte homing [16, 26, 27, 58, 59, 60, 61, 83]. Knowing that N .…”

“…However, several studies have noted the presence of different components in these venoms, including phospholipases A 2 (PLA 2 ), hyaluronidases (HYA) [13, 14, 15], metallo- (SVMP) and serine proteinases (SVSP) [16, 17, 18], inhibitors [19], peptides [20] and cytotoxins [21, 22]. All of these components may have cytotoxic [14, 23, 24], hemorrhagic, anticoagulant [25], pro-inflammatory [26, 27] or immunogenic [28] properties.…”

Multiple mechanisms underlying neuroprotection by secretory phospholipase A2 preconditioning in a surgically induced brain injury rat model

“…Cobra venom-derived secretory PLA2 (sPLA2) catalyzes the hydrolysis of membrane phospholipids to produce the lipid mediator, arachidonic acid (AA), which is further oxygenated into LTB4 by the enzyme 5-LOX (Ghassemi and Rosenberg, 1992; Rosenberg et al, 1983; Yates et al, 1990). PLA2 isolated from Naja sputatrix venom was reported to induce pulmonary inflammation and edema when administered intravenously and intra-tracheally to rats (Cher et al, 2003). Previous studies show that PLA2 plays a role in the worsening of cerebral ischemic injury in rodent models (Bonventre et al, 1997; Clemens et al, 1996).…”

Naja sputatrix Venom Preconditioning Attenuates Neuroinflammation in a Rat Model of Surgical Brain Injury via PLA2/5-LOX/LTB4 Cascade Activation

“…Secretory PLA2 is the second biggest component of Naja sputatrix (Malayan spitting cobra) venom accounting for 15% of its dry weight only second to polypeptide cardiotoxins which comprise 60% of dry weight of the venom 18–20 . Previous study showed that sPLA2 isolated from Naja sputatrix venom induced pulmonary inflammation and edema when administered to rats 21 . Mice lacking PLA2 when subjected to cerebral ischemia had smaller infarcts, reduced brain edema and neurological deficits 22 .…”