MR-dependent collagen internalization by M2-like macrophages. (A and B) Representative high-magnification image of a high-level internalizing cell of the dermis of wild-type (A) and Mrc1^−/− mice (B). Examples of endocytic vesicle containing collagen and dextran are indicated with arrows. No or very little collagen is observed in endocytic vesicles in the Mrc1^−/− mice (compare A and B). Bars, 10 µm. (C and D) In wild type (C and D, left four bars), littermate Mrc1^−/− mice (C, right four bars), or littermate Mrc2^−/− mice (D, right four bars), the high-level internalizing cells were identified based on their prominent lysosomes and scored for the level of collagen uptake (high, medium, low, or none). n = 4 each for wild type, Mrc1^−/− mice, and Mrc2^−/− mice. (E and F) High-level MR-dependent collagen internalization by M2-like macrophages is recapitulated in vitro. Lysates from human blood monocytes differentiated in vitro to resting macrophages or stimulated to acquire an M1- or M2-polarized phenotype were analyzed by Western blotting for the expression of MR (E). The position of MR is indicated on the right. Positions of molecular mass markers (kilodaltons) are indicated on the left. (F) ¹²⁵I-labeled collagen was added to in vitro–generated M1- and M2-polarized macrophages. After 4 h, the intracellular fraction of each cell sample was isolated, and the amount of internalized collagen was measured. Ab, antibody. Data are shown as means ± SD.