by Joanne L. Pennock, and Richard K. Grencis

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by Joanne L. Pennock, and Richard K. Grencis In vivo exit of c-kit+/CD49dhi/β7+ mucosal mast cell precursors from the bone marrow following infection with the intestinal nematode Trichinella spiralis by Joanne L. Pennock, and Richard K. Grencis Blood Volume 103(7):2655-2660 April 1, 2004 ©2004 by American Society of Hematology

Reduction in mastocytosis using a suboptimal dose of ACK2 in vivo. Reduction in mastocytosis using a suboptimal dose of ACK2 in vivo. Treatment with 125 μg ACK2 resulted in fewer c-kit+ cells in the bone marrow (A) and blood (B) day 5 after infection compared with the IgG-treated group (grayish bars). (C) Mast cells in the small intestine were also reduced (day 10 after infection), n = 4. Joanne L. Pennock, and Richard K. Grencis Blood 2004;103:2655-2660 ©2004 by American Society of Hematology

Mast cell counts and c-kit cell number correlate with worm expulsion. Mast cell counts and c-kit cell number correlate with worm expulsion. (A) NIH mice rapidly expelled T spiralis (histogram) which correlated with an increase in intestinal mastocytosis (line). (B) The total number of cells in the bone marrow reduced during infection (line) as did the total number of c-kit+ cells (histogram); n = 5. Joanne L. Pennock, and Richard K. Grencis Blood 2004;103:2655-2660 ©2004 by American Society of Hematology

C-kit expression in the bone marrow of naive mice. C-kit expression in the bone marrow of naive mice. (A) Nine percent of cells in the bone marrow of naive mice expressed c-kit (G1). These mice could be subdivided into a large granular hemopoietic population (GHP) and a nongranular smaller population (nGHP). (B) All c-kit+ cells coexpressed CD49dhi (α4 integrin) at all time points (ungated data). Joanne L. Pennock, and Richard K. Grencis Blood 2004;103:2655-2660 ©2004 by American Society of Hematology

In vivo treatment with anti-c-kit antibody (ACK2) during T spiralis infection successfully depleted GHP and nGHP c-kit+ cells in the bone marrow. In vivo treatment with anti-c-kit antibody (ACK2) during T spiralis infection successfully depleted GHP and nGHP c-kit+ cells in the bone marrow. (A) Naive mice treated with ACK2 for 8 days. No population changes were observed despite detection of antibody binding. (B) Noticeable population changes in GHP (boxed area) began to occur on day 8 after infection in the ACK2-treated group. (C) Ten days after infection the GHP was severely depleted in the ACK2-treated group. (D) Ex vivo staining with an alternative anti-c-kit antibody (2B8) confirmed the absence of c-kit+ cells in the ACK2-treated group. (E) Cell number recovery on day 10 is due primarily to an increase in B cells. (A-C) Shaded areas indicate IgG-treated group; solid lines, ACK2-treated group. (D-E) Shaded area indicates isotype control; solid line, ACK2-treated group; dashed line, IgG-treated group. Joanne L. Pennock, and Richard K. Grencis Blood 2004;103:2655-2660 ©2004 by American Society of Hematology

A transient cell population could be detected during infection. A transient cell population could be detected during infection. (A) c-kit+/β7+ cells were present in the bone marrow and blood for 24 hours, day 5 after infection (upper right quadrant). These cells were absent in naive and day 6 infected mice. Bone marrow was gated on GHP. Blood ungated. *P < .05. (B) Gating on c-kit/β7+ cells (G1) showed that these cells in the blood and bone marrow have similar size (data taken from the same individual day 5 after infection). (C) The appearance of c-kit+/β7+ cells on day 5 (histogram) preceded the appearance of mature mast cells in the gut (line graph) by 3 days; n = 4. These data represent 1 of 3 separate experiments, and are expressed as means ± SD. Joanne L. Pennock, and Richard K. Grencis Blood 2004;103:2655-2660 ©2004 by American Society of Hematology

Serum SCF peaks between days 4 and 8 after T spiralis infection Serum SCF peaks between days 4 and 8 after T spiralis infection.x Serum SCF as measured by ELISA in ACK2-treated (patterned bars) and IgG-treated groups (shaded bars), n = 5. Serum SCF peaks between days 4 and 8 after T spiralis infection.x Serum SCF as measured by ELISA in ACK2-treated (patterned bars) and IgG-treated groups (shaded bars), n = 5. Joanne L. Pennock, and Richard K. Grencis Blood 2004;103:2655-2660 ©2004 by American Society of Hematology