Inflammation is a major local feature of envenomation by bothropic snakes being characterized by a prominent local edema, pain, and extensive swelling. There are reports demonstrating that whole Bothrops snake venoms and toxins isolated from them are able to activate macrophages functions, such as phagocytosis, production of reactive oxygen, cytokines and eicosanoids, however, little is known about the effects of Bothrops alternatus (B.a.) venom on macrophages. In this work, we evaluated the proinflammatory effects of B.a. venom with in vivo and in vitro experiments using the Raw 264.7 cell line and mouse peritoneal macrophages. We detected that B.a. venom augments cell permeability (2-fold), and cellular extravasation (mainly neutrophils), increase proinflammatory cytokines IL1 (∼300-fold), IL12 (∼200-fold), and TNFα (∼80-fold) liberation and induce the expression of enzymes related to lipid signaling, such as cPLA_2α and COX-2. Additionally, using lipidomic techniques we detected that this venom produces a release of arachidonic acid (∼10 nMol/mg. Protein) and other fatty acids (16:0 and 18:1 n-9c).

Although much of these findings were described in inflammatory processes induced by other bothropic venoms, here we demonstrate that B.a. venom also stimulates pro-inflammatory pathways involving lipid mediators of cell signaling. In this sense, lipidomics analysis of macrophages stimulated with B.a. venom evidenced that the main free fatty acids are implicated in the inflammatory response, and also demonstrated that this venom, is able to activate lipid metabolism even with a low content of PLA₂.

发炎是蛇毒蛇毒的主要局部特征，其特征在于突出的局部水肿，疼痛和广泛的肿胀。有报道表明整个矛头蛇毒和从中分离出的毒素能够激活巨噬细胞的功能，如吞噬作用，产生活性氧，细胞因子和类二十烷酸，但是，知之甚少的影响矛头天牛（巴上）毒液巨噬细胞。在这项工作中，我们评估了Ba的促炎作用。使用Raw 264.7细胞系和小鼠腹膜巨噬细胞进行体内和体外实验的毒液。我们发现爸。毒液可增加细胞通透性（2倍）和细胞外渗（主要是中性粒细胞），增加促炎性细胞因子IL1（约300倍），IL12（约200倍）和TNFα（约80倍）释放并诱导表达有关脂质信号的酶，例如与cPLA _2α和COX-2。此外，使用脂质组学技术，我们检测到这种毒液会释放花生四烯酸（约10 nMol / mg蛋白质）和其他脂肪酸（16：0和18：1 n-9c）。

尽管这些发现中有许多是在其他双臭毒诱发的炎症过程中描述的，但在此我们证明了Ba。毒液还刺激涉及细胞信号转导脂质介体的促炎途径。从这个意义上讲，用Ba刺激的巨噬细胞的脂质组学分析。毒液证明主要的游离脂肪酸与炎症反应有关，并且还证明该毒液即使在PLA ₂含量较低的情况下也能够激活脂质代谢。