*Article* **Modulation of Adhesion Molecules Expression by Different Metalloproteases Isolated from** *Bothrops* **Snakes**

**Bianca C. Zychar 1,\*, Patrícia B. Clissa 2, Eneas Carvalho 3, Adilson S. Alves 4, Cristiani Baldo 5, Eliana L. Faquim-Mauro <sup>2</sup> and Luís Roberto C. Gonçalves 1,\***


**Abstract:** Snake venom metalloproteinases (SVMP) are involved in local inflammatory reactions observed after snakebites. Based on domain composition, they are classified as PI (pro-domain + proteolytic domain), PII (PI + disintegrin-like domains), or PIII (PII + cysteine-rich domains). Here, we studied the role of different SVMPs domains in inducing the expression of adhesion molecules at the microcirculation of the cremaster muscle of mice. We used Jararhagin (Jar)—a PIII SVMP with intense hemorrhagic activity, and Jar-C—a Jar devoid of the catalytic domain, with no hemorrhagic activity, both isolated from *B. jararaca* venom and BnP-1—a weakly hemorrhagic P1 SVMP from *B. neuwiedi* venom. Toxins (0.5 μg) or PBS (100 μL) were injected into the scrotum of mice, and 2, 4, or 24 h later, the protein and gene expression of CD54 and CD31 in the endothelium, and integrins (CD11a and CD11b), expressed in leukocytes were evaluated. Toxins induced significant increases in CD54, CD11a, and CD11b at the initial time and a time-related increase in CD31 expression. In conclusion, our results suggest that, despite differences in hemorrhagic activities and domain composition of the SVMPs used in this study, they behave similarly to the induction of expression of adhesion molecules that promote leukocyte recruitment.

**Keywords:** *Bothrops*; metalloproteases; inflammation; microcirculation; adhesion molecules; leukocyteendothelium interactions

**Key Contribution:** We show that SVMPs with different domain compositions can induce the expression of adhesion molecules into the microvasculature of mouse cremaster muscle; independent of their hemorrhagic activity, which can contribute to the knowledge of local inflammatory reactions observed in *Bothrops* snakebites.
