Disruption of CXCL4/CCL5 heteromer formation decreases the severity of VILI. WT mice were treated with 1 or 3 mg/kg MKEY or scrambled control peptide 15 minutes before the initiation of mechanical ventilation with sham or VILI settings. (A) The paO₂/FiO₂ ratio, (B) neutrophil recruitment into the alveoli, and (C) protein concentration in the BAL were analyzed after 2 hours (n = 4). (D) The formation of circulating platelet-neutrophil aggregates was measured by flow cytometry 30 minutes after induction of sham or VILI ventilation (n = 4). Tyrobp^−/−/Fcer1g^−/− mice or WT mice were treated with busulfan, MKEY, blocking antibodies against CXCL4, CCL5, LFA1, Mac1, or a combination and (E) the paO₂/FiO₂ ratio, (F) neutrophil recruitment into the BAL, and (G) protein concentration in the BAL were analyzed after 2 hours (n = 4). (H) The formation of circulating platelet-neutrophil aggregates was measured by flow cytometry 30 minutes after induction of sham or VILI ventilation (n = 4). *P < .05.