Fate of antigen after intravenous and intraarticular injection into mice. Role of molecular weight and charge.

The role of the charge of differently sized proteins in their penetration, persistence and localization in murine joint tissues was studied. Radiolabeled proteins of variable molecular weight (14-150 kDa) and charge (isoelectric point (pI) 4.5-10) were administered by intravenous and intraarticular routes, and localization studies in the first 2 and at 24 h were done with autoradiography. Small cationic proteins rapidly penetrated joint tissues after intravenous injection and persisted in larger amounts compared to anionic proteins of corresponding size. Small cationic proteins easily penetrated the matrices of both epiphysial and articular cartilage. In contrast larger cationic proteins (cBSA, cIgG) persisted for the greater part in the tissues just around the vessels and cartilage association was less striking. After intraarticular injection it was found that low molecular weight proteins (14 to 47 kDa) are rapidly cleared from the joint. Small cationic proteins persisted somewhat better than anionic ones, but impressive retention was only found with cationic proteins with higher molecular weight (67 to 150 kDa). Our data help to define prerequisite properties of proteins for penetration and interaction with joint structures after systemic supply or local production.