Platelets degrade proinflammatory matrix HA using HYAL2. PolyI:C-stimulated human M-SMCs were co-incubated with untreated freshly isolated human platelets or with HYAL2 blocking antibody–treated platelets for 2 hours at 37°C. (A) ELISA-like assay measurement of the amounts of HA released into the media by M-SMCs. Coincubation of stimulated M-SMCs with HYAL2 antibody–treated platelets resulted in a significant decrease in HA released into media compared with untreated or IgG-treated platelets (n = 3; *P < .05). The inhibiting effect of the HYAL2 blocking antibody was dose dependent. (B) Histochemical staining of M-SMC–associated HA (green) and platelets (red = CD42b) in the absence or presence of HYAL2 antibody. Whereas untreated platelets degraded HA on stimulated M-SMCs, HYAL2 antibody–treated platelets bound HA cables on the surfaces of M-SMCs without degrading them. Image, detection, and software details: Leica TCS SP5 II confocal/multi-photon high-speed upright microscope (Leica), HCX PL APO ×40/1.25NA oil immersion objective, Leica HyD system detector, Leica LAS AF software (Leica). Scale bar: 25 µm.