Acceleration of idiopathic pneumonia syndrome (IPS) in the absence of donor MIP-1α (CCL3) after allogeneic BMT in mice by Angela Panoskaltsis-Mortari, John R. Hermanson, Elizabeth Taras, O. Douglas Wangensteen, Jonathan S. Serody, and Bruce R. Blazar Blood Volume 101(9):3714-3721 May 1, 2003 ©2003 by American Society of Hematology

Acceleration of GVHD-mediated mortality in the absence of donor MIP-1α Acceleration of GVHD-mediated mortality in the absence of donor MIP-1α.Cy/TBI-conditioned B10.BR mice received transplants of C57BL/6 BM (■) plus either MIP-1α+/+ (○) or MIP-1α−/−(●) splenocytes. Acceleration of GVHD-mediated mortality in the absence of donor MIP-1α.Cy/TBI-conditioned B10.BR mice received transplants of C57BL/6 BM (■) plus either MIP-1α+/+ (○) or MIP-1α−/−(●) splenocytes. Recipients of MIP-1α−/− splenocytes had accelerated mortality compared with recipients of MIP-1α+/+ cells. (A) Survival. (B) Weights. Results shown are representative of 2 experiments (n = 10 per group;P < .0007). Angela Panoskaltsis-Mortari et al. Blood 2003;101:3714-3721 ©2003 by American Society of Hematology

Recipients of MIP-1α−/− spleen cells exhibit accelerated lung dysfunction after BMT.Specific lung compliance and total lung capacity were determined at days 3, 5, and 7 after BMT in Cy/TBI-conditioned B10.BR mice receiving C57BL/6 BM plus either MIP-1α+/+ o... Recipients of MIP-1α−/− spleen cells exhibit accelerated lung dysfunction after BMT.Specific lung compliance and total lung capacity were determined at days 3, 5, and 7 after BMT in Cy/TBI-conditioned B10.BR mice receiving C57BL/6 BM plus either MIP-1α+/+ or MIP-1α−/− splenocytes. Mean values are indicated for 6 mice per group, pooled from 2 experiments. *P < .05 vs control. Angela Panoskaltsis-Mortari et al. Blood 2003;101:3714-3721 ©2003 by American Society of Hematology

Recipients of GFP-Tg MIP-1α−/− spleen cells exhibit increased migration into the lung, BALT, and spleen on day 3 after BMT.Lethally irradiated B10.BR (allogeneic) or C57BL/6 (syngeneic) mice received C57BL/6 BM and either GFP-Tg MIP-1α+/+ or GFP-Tg MIP-1α−/... Recipients of GFP-Tg MIP-1α−/− spleen cells exhibit increased migration into the lung, BALT, and spleen on day 3 after BMT.Lethally irradiated B10.BR (allogeneic) or C57BL/6 (syngeneic) mice received C57BL/6 BM and either GFP-Tg MIP-1α+/+ or GFP-Tg MIP-1α−/− spleen cells. Shown are in vivo images (1.9-second exposures) of lung, BALT, and spleen captured at day 1 (Figure 3A) and day 3 (Figure 3B) after BMT with a color camera mounted on a stereomicroscope with a GFP filter (× 10.0 zoom factor and × 0.63 transfer lens). “Control” indicates recipient mice receiving allogeneic BM only; images are similar to those of mice receiving syngeneic BM only. Tissues from 1 mouse (of 3 mice) per group per time point are shown. Angela Panoskaltsis-Mortari et al. Blood 2003;101:3714-3721 ©2003 by American Society of Hematology

Acceleration of donor T-cell expansion in the spleens of recipients of MIP-1α−/− cells.Expression of CD4, CD8, and donor haplotype H2bwas determined using flow cytometry and staining with FITC- and PE-labeled mAbs. Acceleration of donor T-cell expansion in the spleens of recipients of MIP-1α−/− cells.Expression of CD4, CD8, and donor haplotype H2bwas determined using flow cytometry and staining with FITC- and PE-labeled mAbs. Values for individual mice are shown and the mean for each group (n = 6, from 2 experiments) is indicated by a bar. “Total number of cells” refers to the total number of nucleated cells of donor or host origin. *P < .05 vs MIP-1α+/+ group. Angela Panoskaltsis-Mortari et al. Blood 2003;101:3714-3721 ©2003 by American Society of Hematology

Acceleration of T-cell influx in the lungs of recipients of MIP-1α−/− cells.Expression of Mac-1, CD4, CD8, and Gr-1 was determined by immunoperoxidase staining of cryosections with biotinylated mAbs. Acceleration of T-cell influx in the lungs of recipients of MIP-1α−/− cells.Expression of Mac-1, CD4, CD8, and Gr-1 was determined by immunoperoxidase staining of cryosections with biotinylated mAbs. Mean values ± SE are indicated for 6 mice per group, pooled from 3 experiments. *P < .05 vs MIP-1α+/+ group. Angela Panoskaltsis-Mortari et al. Blood 2003;101:3714-3721 ©2003 by American Society of Hematology

Accelerated influx of cytolytic granzyme B+cells in the lungs of recipients of MIP-1α−/− spleen cells.Frequencies of cells expressing granzyme B mRNA were determined by in situ hybridization of cryosections with digoxigenin-labeled antisense RNA probes. Accelerated influx of cytolytic granzyme B+cells in the lungs of recipients of MIP-1α−/− spleen cells.Frequencies of cells expressing granzyme B mRNA were determined by in situ hybridization of cryosections with digoxigenin-labeled antisense RNA probes. (A) Mean values ± SE for 4 mice per group, pooled from 2 experiments. *P < .02 vs MIP-1α+/+recipients. (B) In situ hybridizations for granzyme B for one mouse lung representative of each group shown in panel A for days 3 and 7 after BMT (× 200 magnification). Angela Panoskaltsis-Mortari et al. Blood 2003;101:3714-3721 ©2003 by American Society of Hematology

Decreased expression of MIP-1β and RANTES in BAL fluid of MIP-1α−/− spleen cell recipients on day 7 after allogeneic BMT.Protein levels of MIP-1α, MIP-1β, and RANTES were determined by ELISA. Mean values ± SD are indicated for 6 mice per group, pooled from ... Decreased expression of MIP-1β and RANTES in BAL fluid of MIP-1α−/− spleen cell recipients on day 7 after allogeneic BMT.Protein levels of MIP-1α, MIP-1β, and RANTES were determined by ELISA. Mean values ± SD are indicated for 6 mice per group, pooled from 3 experiments. *P < .05 vs MIP-1α+/+ group. Angela Panoskaltsis-Mortari et al. Blood 2003;101:3714-3721 ©2003 by American Society of Hematology

Decreased systemic levels of the anti-inflammatory cytokine IL-13 in serum of MIP-1α−/− spleen cell recipients on day 7 after allogeneic BMT.Protein levels of IL-13 were determined by ELISA. Mean values ± SD are indicated for 6 mice per group, pooled from 3... Decreased systemic levels of the anti-inflammatory cytokine IL-13 in serum of MIP-1α−/− spleen cell recipients on day 7 after allogeneic BMT.Protein levels of IL-13 were determined by ELISA. Mean values ± SD are indicated for 6 mice per group, pooled from 3 experiments. *P < .05 vs MIP-1α+/+ group. Angela Panoskaltsis-Mortari et al. Blood 2003;101:3714-3721 ©2003 by American Society of Hematology