Systemic peptide inhibitor of transendothelial migration administration attenuates microvascular leukocyte adhesion in an ovalbumin-induced mouse model of allergic inflammation

OBJECTIVE: Allergic rhinitis (AR) is driven by type 2 immune polarization and excessive leukocyte trafficking.Current pharmacotherapies act symptomatically rather than at the level of transendothelial migration (TEM).Peptide inhibitor of TEM (PEPITEM) is a B lymphocyte-derived peptide that engages endothelial cadherin-15 to stimulate sphingosine-1-phosphate secretion and inhibit lymphocyte firm adhesion.Although effective in Type 1 autoimmune and metabolic inflammation, PEPITEM has not been examined in Type 2 allergic disease.To evaluate whether systemic PEPITEM administration attenuates systemic leukocyte trafficking in an ovalbumin (OVA)-induced murine AR model, using desloratadine as a clinically established comparator. METHODS:Thirty-two C57Bl/6 mice (16 males, 16 females; 10-12 weeks; 20-25 g) were randomized to four groups (n=4 per sex per group): control, allergy, allergy+desloratadine (10 mg/kg oral gavage), and allergy+PEPITEM (200 μg/200 μL intraperitoneal).AR was induced by intraperitoneal OVA/alum sensitization (days 1-13) and intranasal 1% OVA challenge (days 22-25).Leukocyte rolling counts, stationary, and adherent leukocytes in mesenteric post-capillary venules were quantified by intravital microscopy (IVM).Peripheral leukocyte differentials were determined by hemogram.One-way analysis of variance was used as the primary analysis.RESULTS: OVA sensitization and challenge increased peripheral lymphocytosis (p=0.0446-0.0059)and eosinophilia (p=0.0019) and significantly elevated stationary leukocytes and adhesion (p=0.0003) in mesenteric venules, while rolling was statistically unchanged.PEPITEM reduced firmly adherent leukocyte density (p<0.05 vs. allergy group) and normalized blood eosinophilia, with effects comparable to those observed in the desloratadine-treated group.Tissue oxidative and inflammatory marker analysis showed limited organ-specific changes; PEPITEM reduced myeloperoxidase activity in the liver (p=0.0158) and colon (p=0.0288),whereas malondialdehyde and glutathione levels were largely unchanged across tissues. CONCLUSION:In this study, systemic PEPITEM administration reduces systemic leukocyte adhesion and several allergic phenotypes during OVA-driven Type 2 inflammation, with effects of similar magnitude to desloratadine.