Development of less severe lung injury in recipients of CCR2-deficient donor cells after allogeneic BMT. Lethally irradiated B6D2F₁ mice received BM transplants from either allogeneic CCR2^+/+ (▪) or CCR2^-/- (▦) or syngeneic (□) donors as described in “Patients, materials, and methods,” and animals were analyzed 6 weeks after BMT. (A) Photomicrographs of lung tissue 6 weeks after BMT (hematoxylineosin [HE]; original magnification, × 200). (B) (C) Lung injury was significantly reduced after allogeneic CCR2^-/- BMT compared with allogeneic CCR2^+/+ controls, whereas target organ injury to liver and gastrointestinal tract (SB = small bowel, LB = large bowel) and survival until time of analysis did not differ. Pathology data are presented from 1 experiment representative of 2; n = 5 to 7 per group; ^**P < .01. (D) (E) BALF cellularity (panel D) and absolute numbers of monocytes/macrophages and CD8⁺ T cells (panel E) were significantly decreased after CCR2^-/- BMT compared with allogeneic CCR2^+/+ BMT controls. Data presented are from 2 experiments representative of 4; n = 6 to 11 per group; ^*P < .05. (F) In addition to the total number of F4/80⁺ cells in the BALF, the percentage of F4/80⁺/CD11b⁺ cells was reduced in recipients of CCR2^-/- BM transplants. (G) CCR2 mRNA in the lungs was decreased 6 weeks after allogeneic CCR2^-/- BMT. (H) Reduced lung pathology and BALF cellularity correlated with significantly decreased levels of TNF-α and sTNFRI in the BAL fluid. Data are pooled from 3 experiments; data are presented as mean ± SEM; n = 10 to 17 per group; ^*P < .05. (I) Lung pathology and BALF cellularity are reduced following allogeneic BMT with CCR2^-/- cells compared with allogeneic controls in isolated major histocompatibility complex (MHC) class I and class II disparate BMT systems. Data are presented as mean ± SEM and are from 1 of 2 comparable experiments; n = 3 to 5 per group;^*P < .05.