Differential Macrophage Subsets in Muscle Damage Induced by a K49-PLA 2 from Bothrops jararacussu Venom Modulate the Time Course of the Regeneration Process

• Published in: Inflammation Vol. 42; no. 5; p. 1542
• Main Authors: Ranéia E Silva, Priscila Andrade, da Costa Neves, Adriana, da Rocha, Cristiani Baldo, Moura-da-Silva, Ana Maria, Faquim-Mauro, Eliana L
• Format: Journal Article
• Language: English
• Published: United States 01.10.2019
• Subjects: Animals; Bothrops; Brazil; Crotalid Venoms - enzymology; Crotalid Venoms - toxicity; Cytokines - metabolism; Macrophages - physiology; Muscle Development - immunology; Muscular Diseases - chemically induced; Phospholipases A2 - immunology; Phospholipases A2 - toxicity; Regeneration - immunology; Regeneration - physiology; Snake Bites - complications; Snake Bites - immunology; Time Factors; Brazil; bothropstoxin-I (BthTX-I); innate immunity; inflammation; muscle regeneration; M1/M2 macrophages
• ISSN: 1573-2576

Bothrops snakes cause around 80% of snakebites in Brazil, with muscle tissue damage as an important consequence, which may cause dysfunction on the affected limb. Bothropstoxin-I (BthTX-I) from Bothrops jararacussu is a K49-phospholipase A , involved in the injury and envenomation's inflammatory response. Immune system components act in the resolution of tissue damage and regeneration. Thus, macrophages exert a crucial role in the elimination of dead tissue and muscle repair. Here, we studied the cellular influx and presence of classical and alternative macrophages (M1 and M2) during muscle injury induced by BthTX-I and the regeneration process. BthTX-I elicited intense inflammatory response characterized by neutrophil migration, then increased influx of M1 macrophages followed by M2 population that declined, resulting in tissue regeneration. The high expressions of TNF-α and IL6 were changed by increased TGF-β expression after BthTX-I injection, coinciding with the iNOs and arginase expression and the peaks of M1 and M2 macrophages in muscle tissue. A coordinated sequence of PAX7, MyoD, and myogenin expression involved in muscle regenerative process appeared after BthTX-I injection. Together, these results demonstrate a direct correlation between the macrophage subsets, cytokine microenvironment, and the myogenesis process. This information may be useful for new envenomation and muscular dysfunction therapies.